A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.
A cyclic GMP-dependent protein kinase subtype that is expressed predominantly in INTESTINES, BRAIN, and KIDNEY. The protein is myristoylated on its N-terminus which may play a role its membrane localization.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.
The rate dynamics in chemical or physical systems.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Agents that inhibit PROTEIN KINASES.
A cyclic AMP-dependent protein kinase subtype primarily found in the CYTOPLASM. They are tetrameric proteins that contain two catalytic subunits and two type I-specific regulatory subunits.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Established cell cultures that have the potential to propagate indefinitely.
A mitosporic Ophiostomataceae fungal genus, whose species Sporothrix schenckii is a well-known animal pathogen. The conidia of this soil fungus may be inhaled causing a primary lung infection, or may infect independently via skin punctures.
Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A species of ciliate protozoa. It is used in biomedical research.
A group of compounds that contain the structure SO2NH2.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.
Specific enzyme subunits that form the active sites of the type I and type II cyclic-AMP protein kinases. Each molecule of enzyme contains two catalytic subunits.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The body of a fungus which is made up of HYPHAE.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
Proteins prepared by recombinant DNA technology.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Phosphoproteins are proteins that have been post-translationally modified with the addition of a phosphate group, usually on serine, threonine or tyrosine residues, which can play a role in their regulation, function, interaction with other molecules, and localization within the cell.
Cyclic nucleotides are closed-chain molecules formed from nucleotides (ATP or GTP) through the action of enzymes called cyclases, functioning as second messengers in various cellular signaling pathways, with cAMP and cGMP being the most prominent members.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
The sum of the weight of all the atoms in a molecule.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
An aspect of protein kinase (EC 2.7.1.37) in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Elements of limited time intervals, contributing to particular results or situations.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.

Modulation of Ca2+/calmodulin-dependent protein kinase II activity by acute and chronic morphine administration in rat hippocampus: differential regulation of alpha and beta isoforms. (1/1822)

Calcium/calmodulin-dependent protein kinase II (CaMK II) has been shown to be involved in the regulation of opioid receptor signaling. The present study showed that acute morphine treatment significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus, with little alteration in the protein level of either alpha or beta isoform of CaMK II. However, chronic morphine treatment, by which rats were observed to develop apparent tolerance to morphine, significantly down-regulated both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II and differentially regulated the expression of alpha and beta isoforms of CaMK II at protein and mRNA levels. Application of naloxone or discontinuation of morphine treatment after chronic morphine administration, which induced the withdrawal syndrome of morphine, resulted in the overshoot of CaMK II (at both protein and mRNA levels) and its kinase activity. The phenomena of overshoot were mainly observed in the beta isoform of CaMK II but not in the alpha isoform. The effects of both acute and chronic morphine treatments on CaMK II could be completely abolished by the concomitant application of naloxone, indicating that the effects of morphine were achieved through activation of opioid receptors. Our data demonstrated that both acute and chronic morphine treatments could effectively modulate the activity and the expression of CaMK II in the hippocampus.  (+info)

Muscarinic stimulation of calcium/calmodulin-dependent protein kinase II in isolated rat pancreatic acini. (2/1822)

AIM: To study whether M3 receptor occupation would lead to activation of calcium/calmodulin-dependent protein kinase II (CaM kinase II). METHODS: In this study, we isolated rat pancreatic acini by collagenase digestion; measured the Ca2+/calmodulin-independent activity of autophosphorylated form of the CaM kinase II both before and after stimulation of the acini with muscarinic secretagogue bethanechol (Bet). RESULTS: Bet stimulated the activation of, or generation of Ca(2+)-independent activity of, this kinase, in a concentration (0.0001-1 mmol.L-1) and time (5-300 s)-dependent manner; with Bet of 100 mumol.L-1, Ca(2+)-independent activity increased from an unstimulated level of 4.5 +/- 0.3 (n = 4) to 8.9 +/- 1.3 (n = 4, P < 0.05) at 5 s. Another Ca2+ mobilizing secretagogue cholecystokinin (CCK) also activated the kinase; at 1 mumol.L-1, CCK increased Ca(2+)-independent kinase activity to 12.9 +/- 0.5 (n = 6, P < 0.05). Vasoactive intestinal peptide (VIP) at 1 mumol.L-1 did not produce significant Ca(2+)-independent kinase activity (from control 3.90 +/- 0.28 to 4.53 +/- 0.47, n = 6, P > 0.05). Atropine completely blocked Bet activation of the kinase. CONCLUSION: CaM kinase II plays a pivotal role in digestive enzyme secretion, especially during the initial phase of amylase secretion.  (+info)

Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells. (3/1822)

The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B protein kinase and triggers mitosis. Although the active p34-cyclin B protein kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated the possibility that other kinases may initially trigger the phosphorylation and activation of p54(cdc25-c). We have examined the effects of the calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II) or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II) results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25-c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is no increase in histone H1 kinase activity. Our data suggest that a calcium-calmodulin-dependent step may be involved in the initial activation of p54(cdc25-c).  (+info)

Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor. (4/1822)

The molecular basis of long-term potentiation (LTP), a long-lasting change in synaptic transmission, is of fundamental interest because of its implication in learning. Usually LTP depends on Ca2+ influx through postsynaptic N-methyl-D-aspartate (NMDA)-type glutamate receptors and subsequent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). For a molecular understanding of LTP it is crucial to know how CaMKII is localized to its postsynaptic targets because protein kinases often are targeted to their substrates by adapter proteins. Here we show that CaMKII directly binds to the NMDA receptor subunits NR1 and NR2B. Moreover, activation of CaMKIIalpha by stimulation of NMDA receptors in forebrain slices increase this association. This interaction places CaMKII not only proximal to a major source of Ca2+ influx but also close to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, which become phosphorylated upon stimulation of NMDA receptors in these forebrain slices. Identification of the postsynaptic adapter for CaMKII fills a critical gap in the understanding of LTP because CaMKII-mediated phosphorylation of AMPA receptors is an important step during LTP.  (+info)

Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. (5/1822)

The ability of central glutamatergic synapses to change their strength in response to the intensity of synaptic input, which occurs, for example, in long-term potentiation (LTP), is thought to provide a cellular basis for memory formation and learning. LTP in the CA1 field of the hippocampus requires activation of Ca2+/calmodulin-kinase II (CaM-KII), which phosphorylates Ser-831 in the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptor (AMPA-R), and this activation/phosphorylation is thought to be a postsynaptic mechanism in LTP. In this study, we have identified a molecular mechanism by which CaM-KII potentiates AMPA-Rs. Coexpression in HEK-293 cells of activated CaM-KII with GluR1 did not affect the glutamate affinity of the receptor, the kinetics of desensitization and recovery, channel rectification, open probability, or gating. Single-channel recordings identified multiple conductance states for GluR1, and coexpression with CaM-KII or a mutation of Ser-831 to Asp increased the contribution of the higher conductance states. These results indicate that CaM-KII can mediate plasticity at glutamatergic synapses by increasing single-channel conductance of existing functional AMPA-Rs or by recruiting new high-conductance-state AMPA-Rs.  (+info)

Site-specific phosphorylation of synapsin I by Ca2+/calmodulin-dependent protein kinase II in pancreatic betaTC3 cells: synapsin I is not associated with insulin secretory granules. (6/1822)

Increasing evidence supports a physiological role of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in the secretion of insulin from the pancreatic beta-cell, but the precise sites of action are not known. A role of this enzyme in neuroexocytosis is implicated by its phosphorylation of a vesicle-associated protein, synapsin I. Because of emerging similarities to the neuron with respect to exocytotic mechanisms, the expression and phosphorylation of synapsin I in the beta-cell have been studied. Synapsin I expression in clonal mouse beta-cells (betaTC3) and primary rat islet beta-cells was initially confirmed by immunoblot analysis. By immunoprecipitation, in situ phosphorylation of synapsin I was induced in permeabilized betaTC3 cells within a Ca2+ concentration range shown to activate endogenous CaM kinase II under identical conditions. Proteolytic digests of these immunoprecipitates revealed that calcium primarily induced the increased phosphorylation of sites identified as CaM kinase II-specific and distinct from protein kinase A-specific sites. Immunofluorescence and immunogold electron microscopy verified synapsin I expression in betaTC3 cells and pancreatic slices but demonstrated little if any colocalization of synapsin I with insulin-containing dense core granules. Thus, although this study establishes that synapsin I is a substrate for CaM kinase II in the pancreatic beta-cell, this event appears not to be important for the mobilization of insulin granules.  (+info)

Current studies on a working model of CaM kinase II in hippocampal long-term potentiation and memory. (7/1822)

There have been recent advances in understanding the molecular basis of the long-term potentiation (LTP) of synaptic transmission in the hippocampus. This review documents current views on mechanisms underlying LTP induction, from activation of the NMDA receptor to stimulation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). We will focus in particular on recent findings of how CaM kinase II encodes the frequency of synaptic usage and serves as a molecular memory switch at the synapse. Furthermore, a role for CaM kinase II in spatial learning and memory is demonstrated by recent studies using transgenic mice.  (+info)

Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca2+/calmodulin-dependent protein kinases in cultured rat hippocampal neurons. (8/1822)

Calcium/calmodulin-dependent protein kinases (CaM kinases) are major multifunctional enzymes that play important roles in calcium-mediated signal transduction. To characterize their regulatory mechanisms in neurons, we compared glutamate-induced phosphorylation of CaM kinase IV and CaM kinase II in cultured rat hippocampal neurons. We observed that dephosphorylation of these kinases followed different time courses, suggesting different regulatory mechanisms for each kinase. Okadaic acid, an inhibitor of protein phosphatase (PP) 1 and PP2A, increased the phosphorylation of both kinases. In contrast, cyclosporin A, an inhibitor of calcineurin, showed different effects: the phosphorylation and activity of CaM kinase IV were significantly increased with this inhibitor, but those of CaM kinase II were not significantly increased. Cyclosporin A treatment of neurons increased phosphorylation of Thr196 of CaM kinase IV, the activated form with CaM kinase kinase, which was recognized with an anti-phospho-Thr196 antibody. Moreover, recombinant CaM kinase IV was dephosphorylated and inactivated with calcineurin as well as with PP1, PP2A, and PP2C in vitro. These results suggest that CaM kinase IV, but not CaM kinase II, is directly regulated with calcineurin.  (+info)

Calcium-calmodulin-dependent protein kinase type 2 (CAMK2) is a type of serine/threonine protein kinase that plays a crucial role in signal transduction pathways related to synaptic plasticity, learning, and memory. It is composed of four subunits, each with a catalytic domain and a regulatory domain that contains an autoinhibitory region and a calmodulin-binding site.

The activation of CAMK2 requires the binding of calcium ions (Ca^2+^) to calmodulin, which then binds to the regulatory domain of CAMK2, relieving the autoinhibition and allowing the kinase to phosphorylate its substrates. Once activated, CAMK2 can also undergo a process called autophosphorylation, which results in a persistent activation state that can last for hours or even days.

CAMK2 has many downstream targets, including ion channels, transcription factors, and other protein kinases. Dysregulation of CAMK2 signaling has been implicated in various neurological disorders, such as Alzheimer's disease, Parkinson's disease, and epilepsy.

Calcium-calmodulin-dependent protein kinases (CAMKs) are a family of enzymes that play a crucial role in intracellular signaling pathways. They are activated by the binding of calcium ions and calmodulin, a ubiquitous calcium-binding protein, to their regulatory domain.

Once activated, CAMKs phosphorylate specific serine or threonine residues on target proteins, thereby modulating their activity, localization, or stability. This post-translational modification is essential for various cellular processes, including synaptic plasticity, gene expression, metabolism, and cell cycle regulation.

There are several subfamilies of CAMKs, including CaMKI, CaMKII, CaMKIII (also known as CaMKIV), and CaMK kinase (CaMKK). Each subfamily has distinct structural features, substrate specificity, and regulatory mechanisms. Dysregulation of CAMK signaling has been implicated in various pathological conditions, such as neurodegenerative diseases, cancer, and cardiovascular disorders.

Calmodulin is a small, ubiquitous calcium-binding protein that plays a critical role in various intracellular signaling pathways. It functions as a calcium sensor, binding to and regulating the activity of numerous target proteins upon calcium ion (Ca^2+^) binding. Calmodulin is expressed in all eukaryotic cells and participates in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, metabolism, and cell cycle progression.

The protein contains four EF-hand motifs that can bind Ca^2+^ ions. Upon calcium binding, conformational changes occur in the calmodulin structure, exposing hydrophobic surfaces that facilitate its interaction with target proteins. Calmodulin's targets include enzymes (such as protein kinases and phosphatases), ion channels, transporters, and cytoskeletal components. By modulating the activity of these proteins, calmodulin helps regulate essential cellular functions in response to changes in intracellular Ca^2+^ concentrations.

Calmodulin's molecular weight is approximately 17 kDa, and it consists of a single polypeptide chain with 148-150 amino acid residues. The protein can be found in both the cytoplasm and the nucleus of cells. In addition to its role as a calcium sensor, calmodulin has been implicated in various pathological conditions, including cancer, neurodegenerative diseases, and cardiovascular disorders.

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase type I (PKG I) is a major enzyme responsible for mediating the effects of cGMP, which is a second messenger molecule involved in various cellular signaling pathways. PKG I is a serine/threonine protein kinase that is activated by binding to cGMP.

PKG I exists in two isoforms, alpha and beta, which are encoded by separate genes but share a similar structure and function. The enzyme consists of a regulatory domain, which contains the cGMP-binding sites, and a catalytic domain, which carries out the phosphorylation of target proteins.

PKG I plays a critical role in regulating various physiological processes, including smooth muscle relaxation, cardiac contractility, platelet aggregation, and neuronal signaling. It does so by phosphorylating specific protein targets that control these processes, such as ion channels, enzymes, and cytoskeletal proteins.

Defects in PKG I function have been implicated in several human diseases, including pulmonary hypertension, heart failure, and erectile dysfunction. Therefore, PKG I is an important therapeutic target for the development of drugs to treat these conditions.

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase type II (PKG II) is a subtype of cGMP-dependent protein kinases, which are enzymes that play a crucial role in the regulation of various cellular functions. PKG II is specifically expressed in certain tissues such as the smooth muscle and the brain.

The activation of PKG II occurs when cGMP binds to the regulatory subunit of the enzyme, leading to the release and activation of the catalytic subunit. Once activated, PKG II phosphorylates specific serine and threonine residues on target proteins, which in turn modulate their activity, localization, or stability.

PKG II has been implicated in several physiological processes, including smooth muscle relaxation, platelet aggregation, neuronal signaling, and cardiovascular function. Dysregulation of PKG II has been associated with various pathological conditions such as hypertension, pulmonary arterial hypertension, heart failure, and neurodegenerative disorders.

Calcium-calmodulin-dependent protein kinase type 4 (CAMK4) is a type of serine/threonine protein kinase that plays a crucial role in signal transduction pathways related to synaptic plasticity, learning, and memory. It is activated by the binding of calcium ions and calmodulin, a regulatory protein that binds calcium ions, to its calcium-calmodulin binding domain.

Once activated, CAMK4 phosphorylates various downstream target proteins, including transcription factors, ion channels, and other kinases, thereby modulating their activities. This enzyme is widely expressed in various tissues, but it is particularly abundant in the brain, where it has been implicated in long-term potentiation (LTP), a form of synaptic plasticity that underlies learning and memory.

Mutations or dysregulation of CAMK4 have been associated with several neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Therefore, understanding the molecular mechanisms underlying CAMK4 activation and regulation is an important area of research in neuroscience and pharmacology.

Protein kinases are a group of enzymes that play a crucial role in many cellular processes by adding phosphate groups to other proteins, a process known as phosphorylation. This modification can activate or deactivate the target protein's function, thereby regulating various signaling pathways within the cell. Protein kinases are essential for numerous biological functions, including metabolism, signal transduction, cell cycle progression, and apoptosis (programmed cell death). Abnormal regulation of protein kinases has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) are a type of enzyme that add phosphate groups to other proteins, thereby modifying their function. These kinases are activated by cGMP, which is a second messenger molecule that helps transmit signals within cells. PKGs play important roles in various cellular processes, including smooth muscle relaxation, platelet aggregation, and cardiac contractility. They have been implicated in the regulation of a number of physiological functions, such as blood flow, inflammation, and learning and memory. There are two main isoforms of cGMP-dependent protein kinases, PKG I and PKG II, which differ in their tissue distribution, regulatory properties, and substrate specificity.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Cyclic AMP-dependent protein kinase type II (PKA II) is a subtype of cyclic AMP (cAMP)-dependent protein kinase, which is a crucial enzyme in many cellular processes. PKA II is composed of two regulatory subunits and two catalytic subunits. When cAMP levels are low, the regulatory subunits bind to and inhibit the catalytic subunits. However, when cAMP levels rise, cAMP molecules bind to the regulatory subunits, causing a conformational change that releases and activates the catalytic subunits.

The activated catalytic subunits then phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity, localization, or stability. PKA II is widely expressed in various tissues and plays a role in regulating diverse cellular functions such as metabolism, gene expression, cell growth, differentiation, and apoptosis.

PKA II is distinct from the other subtype of cAMP-dependent protein kinase, PKA I, in its regulatory subunit composition and tissue distribution. While both PKA I and PKA II contain identical catalytic subunits, they differ in their regulatory subunits: PKA I contains the RIα, RIβ, or RIIβ regulatory subunits, while PKA II contains the RIIα regulatory subunit. Additionally, PKA II is predominantly expressed in tissues such as the brain, heart, and skeletal muscle, whereas PKA I is more widely distributed throughout the body.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Cyclic AMP (cAMP)-dependent protein kinases, also known as protein kinase A (PKA), are a family of enzymes that play a crucial role in intracellular signaling pathways. These enzymes are responsible for the regulation of various cellular processes, including metabolism, gene expression, and cell growth and differentiation.

PKA is composed of two regulatory subunits and two catalytic subunits. When cAMP binds to the regulatory subunits, it causes a conformational change that leads to the dissociation of the catalytic subunits. The freed catalytic subunits then phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity.

The cAMP-dependent protein kinases are activated in response to a variety of extracellular signals, such as hormones and neurotransmitters, that bind to G protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs). These signals lead to the activation of adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The resulting increase in intracellular cAMP levels triggers the activation of PKA and the downstream phosphorylation of target proteins.

Overall, cAMP-dependent protein kinases are essential regulators of many fundamental cellular processes and play a critical role in maintaining normal physiology and homeostasis. Dysregulation of these enzymes has been implicated in various diseases, including cancer, diabetes, and neurological disorders.

Calcium-calmodulin-dependent protein kinase type 1 (CAMK1) is a type of serine/threonine protein kinase that plays a crucial role in signal transduction pathways involved in various cellular processes, including synaptic plasticity, learning, and memory. It is activated by the binding of calcium ions (Ca2+) and calmodulin, a ubiquitous calcium-binding protein, to its regulatory domain.

Once activated, CAMK1 phosphorylates various downstream target proteins, leading to changes in their activity or function. In the brain, CAMK1 is primarily expressed in neurons and has been implicated in the regulation of synaptic strength and transmission, as well as in the modulation of gene expression and cell survival. Dysregulation of CAMK1 has been associated with several neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy.

Benzylamines are a class of organic compounds that consist of a benzene ring attached to an amine group. The amine group (-NH2) can be primary, secondary, or tertiary, depending on the number of hydrogen atoms bonded to the nitrogen atom. Benzylamines are used in the synthesis of various pharmaceuticals, agrochemicals, and other organic compounds. They have a variety of biological activities and can act as central nervous system depressants, local anesthetics, and muscle relaxants. However, some benzylamines can also be toxic or carcinogenic, so they must be handled with care.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

Cyclic adenosine monophosphate (cAMP) is a key secondary messenger in many biological processes, including the regulation of metabolism, gene expression, and cellular excitability. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase and is degraded by the enzyme phosphodiesterase.

In the body, cAMP plays a crucial role in mediating the effects of hormones and neurotransmitters on target cells. For example, when a hormone binds to its receptor on the surface of a cell, it can activate a G protein, which in turn activates adenylyl cyclase to produce cAMP. The increased levels of cAMP then activate various effector proteins, such as protein kinases, which go on to regulate various cellular processes.

Overall, the regulation of cAMP levels is critical for maintaining proper cellular function and homeostasis, and abnormalities in cAMP signaling have been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.

Calcium signaling is the process by which cells regulate various functions through changes in intracellular calcium ion concentrations. Calcium ions (Ca^2+^) are crucial second messengers that play a critical role in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, and programmed cell death (apoptosis).

Intracellular calcium levels are tightly regulated by a complex network of channels, pumps, and exchangers located on the plasma membrane and intracellular organelles such as the endoplasmic reticulum (ER) and mitochondria. These proteins control the influx, efflux, and storage of calcium ions within the cell.

Calcium signaling is initiated when an external signal, such as a hormone or neurotransmitter, binds to a specific receptor on the plasma membrane. This interaction triggers the opening of ion channels, allowing extracellular Ca^2+^ to flow into the cytoplasm. In some cases, this influx of calcium ions is sufficient to activate downstream targets directly. However, in most instances, the increase in intracellular Ca^2+^ serves as a trigger for the release of additional calcium from internal stores, such as the ER.

The release of calcium from the ER is mediated by ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), which are activated by specific second messengers generated in response to the initial external signal. The activation of these channels leads to a rapid increase in cytoplasmic Ca^2+^, creating a transient intracellular calcium signal known as a "calcium spark" or "calcium puff."

These localized increases in calcium concentration can then propagate throughout the cell as waves of elevated calcium, allowing for the spatial and temporal coordination of various cellular responses. The duration and amplitude of these calcium signals are finely tuned by the interplay between calcium-binding proteins, pumps, and exchangers, ensuring that appropriate responses are elicited in a controlled manner.

Dysregulation of intracellular calcium signaling has been implicated in numerous pathological conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer. Therefore, understanding the molecular mechanisms governing calcium homeostasis and signaling is crucial for the development of novel therapeutic strategies targeting these diseases.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Cyclic AMP-dependent protein kinase RIα subunit, also known as PKA RIα or PRKAR1A, is a type of regulatory subunit of the cyclic AMP (cAMP)-dependent protein kinase (PKA) enzyme. PKA is a key enzyme in many cellular signaling pathways and is composed of two regulatory subunits and two catalytic subunits. The RIα subunit is one of the four different regulatory subunits (RIα, RIβ, RIIα, and RIIβ) that regulate PKA activity by binding to cAMP, which leads to the release and activation of the catalytic subunits.

The RIα subunit is encoded by the PRKAR1A gene and is primarily expressed in many tissues, including the brain, heart, and adrenal glands. Mutations in the PRKAR1A gene have been associated with several genetic disorders, such as Carney Complex, a rare autosomal dominant disorder characterized by multiple tumors and endocrine overactivity. The RIα subunit plays an essential role in regulating various cellular processes, including metabolism, differentiation, proliferation, and apoptosis.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Protein kinase inhibitors (PKIs) are a class of drugs that work by interfering with the function of protein kinases. Protein kinases are enzymes that play a crucial role in many cellular processes by adding a phosphate group to specific proteins, thereby modifying their activity, localization, or interaction with other molecules. This process of adding a phosphate group is known as phosphorylation and is a key mechanism for regulating various cellular functions, including signal transduction, metabolism, and cell division.

In some diseases, such as cancer, protein kinases can become overactive or mutated, leading to uncontrolled cell growth and division. Protein kinase inhibitors are designed to block the activity of these dysregulated kinases, thereby preventing or slowing down the progression of the disease. These drugs can be highly specific, targeting individual protein kinases or families of kinases, making them valuable tools for targeted therapy in cancer and other diseases.

Protein kinase inhibitors can work in various ways to block the activity of protein kinases. Some bind directly to the active site of the enzyme, preventing it from interacting with its substrates. Others bind to allosteric sites, changing the conformation of the enzyme and making it inactive. Still, others target upstream regulators of protein kinases or interfere with their ability to form functional complexes.

Examples of protein kinase inhibitors include imatinib (Gleevec), which targets the BCR-ABL kinase in chronic myeloid leukemia, and gefitinib (Iressa), which inhibits the EGFR kinase in non-small cell lung cancer. These drugs have shown significant clinical benefits in treating these diseases and have become important components of modern cancer therapy.

Cyclic AMP-dependent protein kinase type I (PKA) is a key enzyme in intracellular signaling pathways that is activated by the second messenger cyclic adenosine monophosphate (cAMP). PKA is composed of two regulatory subunits and two catalytic subunits, which are held in an inactive state by binding to cAMP. When cAMP levels increase, it binds to the regulatory subunits, causing them to dissociate from the catalytic subunits and allowing the catalytic subunits to phosphorylate and activate target proteins.

PKA plays a critical role in many physiological processes, including metabolism, gene expression, cell growth and differentiation, and synaptic plasticity. Dysregulation of PKA signaling has been implicated in various diseases, such as cancer, cardiovascular disease, and neurological disorders. Therefore, understanding the mechanisms that regulate PKA activity is crucial for developing therapeutic strategies to target these conditions.

Cyclic guanosine monophosphate (cGMP) is a important second messenger molecule that plays a crucial role in various biological processes within the human body. It is synthesized from guanosine triphosphate (GTP) by the enzyme guanylyl cyclase.

Cyclic GMP is involved in regulating diverse physiological functions, such as smooth muscle relaxation, cardiovascular function, and neurotransmission. It also plays a role in modulating immune responses and cellular growth and differentiation.

In the medical field, changes in cGMP levels or dysregulation of cGMP-dependent pathways have been implicated in various disease states, including pulmonary hypertension, heart failure, erectile dysfunction, and glaucoma. Therefore, pharmacological agents that target cGMP signaling are being developed as potential therapeutic options for these conditions.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

"Sporothrix" is a genus of fungi that includes several species, the most well-known of which is "Sporothrix schenckii." This particular species is an environmental saprophyte, commonly found in soil, plant matter, and decaying organic material. It can cause a disease in humans and animals known as sporotrichosis, which is a subcutaneous infection that typically affects the skin and underlying tissue. The infection usually occurs after traumatic inoculation of the fungus through the skin, often from activities such as gardening or handling contaminated plant material.

The infection initially presents as a painless, nodular lesion at the site of inoculation, which can later ulcerate and spread to other parts of the body through lymphatic channels. Disseminated sporotrichosis is rare but can occur in immunocompromised individuals, affecting various organs such as the lungs, bones, and central nervous system.

Proper diagnosis of sporotrichosis involves direct examination and culture of clinical specimens, as well as serological tests and molecular techniques. Treatment typically includes oral antifungal medications such as itraconazole or posaconazole, although amphotericin B may be required in severe cases or in patients with compromised immune systems.

Calmodulin-binding proteins are a diverse group of proteins that have the ability to bind to calmodulin, a ubiquitous calcium-binding protein found in eukaryotic cells. Calmodulin plays a critical role in various cellular processes by regulating the activity of its target proteins in a calcium-dependent manner.

Calmodulin-binding proteins contain specific domains or motifs that enable them to interact with calmodulin. These domains can be classified into two main categories: IQ motifs and CaM motifs. The IQ motif is a short amino acid sequence that contains the consensus sequence IQXXXRGXXR, where X represents any amino acid. This motif binds to the C-lobe of calmodulin in a calcium-dependent manner. On the other hand, CaM motifs are longer sequences that can bind to both lobes of calmodulin with high affinity and in a calcium-dependent manner.

Calmodulin-binding proteins play crucial roles in various cellular functions, including signal transduction, gene regulation, cytoskeleton organization, and ion channel regulation. For example, calmodulin-binding proteins such as calcineurin and CaM kinases are involved in the regulation of immune responses, learning, and memory. Similarly, myosin regulatory light chains, which contain IQ motifs, play a critical role in muscle contraction by regulating the interaction between actin and myosin filaments.

In summary, calmodulin-binding proteins are a diverse group of proteins that interact with calmodulin to regulate various cellular processes. They contain specific domains or motifs that enable them to bind to calmodulin in a calcium-dependent manner, thereby modulating the activity of their target proteins.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Mitogen-Activated Protein Kinases (MAPKs) are a family of serine/threonine protein kinases that play crucial roles in various cellular processes, including proliferation, differentiation, transformation, and apoptosis, in response to diverse stimuli such as mitogens, growth factors, hormones, cytokines, and environmental stresses. They are highly conserved across eukaryotes and consist of a three-tiered kinase module composed of MAPK kinase kinases (MAP3Ks), MAPK kinases (MKKs or MAP2Ks), and MAPKs.

Activation of MAPKs occurs through a sequential phosphorylation and activation cascade, where MAP3Ks phosphorylate and activate MKKs, which in turn phosphorylate and activate MAPKs at specific residues (Thr-X-Tyr or Ser-Pro motifs). Once activated, MAPKs can further phosphorylate and regulate various downstream targets, including transcription factors and other protein kinases.

There are four major groups of MAPKs in mammals: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5/BMK1. Each group of MAPKs has distinct upstream activators, downstream targets, and cellular functions, allowing for a high degree of specificity in signal transduction and cellular responses. Dysregulation of MAPK signaling pathways has been implicated in various human diseases, including cancer, diabetes, neurodegenerative disorders, and inflammatory diseases.

I apologize for any confusion, but "Paramecium tetraurelia" is not a medical term. It is the scientific name of a species of ciliate protists, which are single-celled organisms commonly found in freshwater environments. These organisms are often studied in biology and microbiology as models for cellular and molecular processes. If you have any questions related to medical terminology or definitions, I would be happy to help with those instead.

Sulfonamides are a group of synthetic antibacterial drugs that contain the sulfonamide group (SO2NH2) in their chemical structure. They are bacteriostatic agents, meaning they inhibit bacterial growth rather than killing them outright. Sulfonamides work by preventing the bacteria from synthesizing folic acid, which is essential for their survival.

The first sulfonamide drug was introduced in the 1930s and since then, many different sulfonamides have been developed with varying chemical structures and pharmacological properties. They are used to treat a wide range of bacterial infections, including urinary tract infections, respiratory tract infections, skin and soft tissue infections, and ear infections.

Some common sulfonamide drugs include sulfisoxazole, sulfamethoxazole, and trimethoprim-sulfamethoxazole (a combination of a sulfonamide and another antibiotic called trimethoprim). While sulfonamides are generally safe and effective when used as directed, they can cause side effects such as rash, nausea, and allergic reactions. It is important to follow the prescribing physician's instructions carefully and to report any unusual symptoms or side effects promptly.

Calcium-binding proteins (CaBPs) are a diverse group of proteins that have the ability to bind calcium ions (Ca^2+^) with high affinity and specificity. They play crucial roles in various cellular processes, including signal transduction, muscle contraction, neurotransmitter release, and protection against oxidative stress.

The binding of calcium ions to these proteins induces conformational changes that can either activate or inhibit their functions. Some well-known CaBPs include calmodulin, troponin C, S100 proteins, and parvalbumins. These proteins are essential for maintaining calcium homeostasis within cells and for mediating the effects of calcium as a second messenger in various cellular signaling pathways.

Trifluoperazine is an antipsychotic medication that belongs to the class of drugs called phenothiazines. It works by blocking the action of dopamine, a neurotransmitter in the brain, and helps to reduce symptoms of schizophrenia such as hallucinations, delusions, paranoia, and disordered thought. Trifluoperazine may also be used to manage anxiety or agitation in certain medical conditions. It is available in the form of tablets for oral administration. As with any medication, trifluoperazine should be taken under the supervision of a healthcare provider due to potential side effects and risks associated with its use.

Mitogen-activated protein kinase (MAPK) signaling system is a crucial pathway for the transmission and regulation of various cellular responses in eukaryotic cells. It plays a significant role in several biological processes, including proliferation, differentiation, apoptosis, inflammation, and stress response. The MAPK cascade consists of three main components: MAP kinase kinase kinase (MAP3K or MEKK), MAP kinase kinase (MAP2K or MEK), and MAP kinase (MAPK).

The signaling system is activated by various extracellular stimuli, such as growth factors, cytokines, hormones, and stress signals. These stimuli initiate a phosphorylation cascade that ultimately leads to the activation of MAPKs. The activated MAPKs then translocate into the nucleus and regulate gene expression by phosphorylating various transcription factors and other regulatory proteins.

There are four major MAPK families: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5. Each family has distinct functions, substrates, and upstream activators. Dysregulation of the MAPK signaling system can lead to various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the molecular mechanisms underlying this pathway is crucial for developing novel therapeutic strategies.

"Cattle" is a term used in the agricultural and veterinary fields to refer to domesticated animals of the genus *Bos*, primarily *Bos taurus* (European cattle) and *Bos indicus* (Zebu). These animals are often raised for meat, milk, leather, and labor. They are also known as bovines or cows (for females), bulls (intact males), and steers/bullocks (castrated males). However, in a strict medical definition, "cattle" does not apply to humans or other animals.

Myosin-Light-Chain Kinase (MLCK) is an enzyme that plays a crucial role in muscle contraction. It phosphorylates the regulatory light chains of myosin, a protein involved in muscle contraction, leading to the activation of myosin and the initiation of the contractile process. MLCK is activated by calcium ions and calmodulin, and its activity is essential for various cellular processes, including cytokinesis, cell motility, and maintenance of cell shape. In addition to its role in muscle contraction, MLCK has been implicated in several pathological conditions, such as hypertension, atherosclerosis, and cancer.

Phosphatidylinositol 3-Kinases (PI3Ks) are a family of enzymes that play a crucial role in intracellular signal transduction. They phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol and its derivatives, which results in the production of second messengers that regulate various cellular processes such as cell growth, proliferation, differentiation, motility, and survival.

PI3Ks are divided into three classes based on their structure and substrate specificity. Class I PI3Ks are further subdivided into two categories: class IA and class IB. Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, p55γ, or p50γ). They are primarily activated by receptor tyrosine kinases and G protein-coupled receptors. Class IB PI3Ks consist of a catalytic subunit (p110γ) and a regulatory subunit (p101 or p84/87). They are mainly activated by G protein-coupled receptors.

Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders. Therefore, PI3Ks have emerged as important targets for drug development in these areas.

p38 Mitogen-Activated Protein Kinases (p38 MAPKs) are a family of conserved serine-threonine protein kinases that play crucial roles in various cellular processes, including inflammation, immune response, differentiation, apoptosis, and stress responses. They are activated by diverse stimuli such as cytokines, ultraviolet radiation, heat shock, osmotic stress, and lipopolysaccharides (LPS).

Once activated, p38 MAPKs phosphorylate and regulate several downstream targets, including transcription factors and other protein kinases. This regulation leads to the expression of genes involved in inflammation, cell cycle arrest, and apoptosis. Dysregulation of p38 MAPK signaling has been implicated in various diseases, such as cancer, neurodegenerative disorders, and autoimmune diseases. Therefore, p38 MAPKs are considered promising targets for developing new therapeutic strategies to treat these conditions.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

eIF-2 kinase is a type of protein kinase that phosphorylates the alpha subunit of eukaryotic initiation factor-2 (eIF-2) at serine 51. This phosphorylation event inhibits the guanine nucleotide exchange factor eIF-2B, thereby preventing the recycling of eIF-2 and reducing global protein synthesis.

There are four main subtypes of eIF-2 kinases:

1. HRI (heme-regulated inhibitor) - responds to heme deficiency and oxidative stress
2. PERK (PKR-like endoplasmic reticulum kinase) - activated by ER stress and misfolded proteins in the ER
3. GCN2 (general control non-derepressible 2) - responds to amino acid starvation
4. PKR (double-stranded RNA-activated protein kinase) - activated by double-stranded RNA during viral infections

These eIF-2 kinases play crucial roles in regulating cellular responses to various stress conditions, such as the integrated stress response (ISR), which helps maintain cellular homeostasis and promote survival under adverse conditions.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

Tetradecanoylphorbol acetate (TPA) is defined as a pharmacological agent that is a derivative of the phorbol ester family. It is a potent tumor promoter and activator of protein kinase C (PKC), a group of enzymes that play a role in various cellular processes such as signal transduction, proliferation, and differentiation. TPA has been widely used in research to study PKC-mediated signaling pathways and its role in cancer development and progression. It is also used in topical treatments for skin conditions such as psoriasis.

Protein Kinase C-alpha (PKC-α) is a specific isoform of the Protein Kinase C (PKC) family, which are serine/threonine protein kinases that play crucial roles in various cellular processes such as proliferation, differentiation, and apoptosis. PKC-α is activated by diacylglycerol (DAG) and calcium ions (Ca2+). It is involved in signal transduction pathways related to cell growth, differentiation, and oncogenic transformation. Mutations or dysregulation of PKC-alpha have been implicated in several diseases including cancer, diabetes, and neurological disorders.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

Pyruvate kinase is an enzyme that plays a crucial role in the final step of glycolysis, a process by which glucose is broken down to produce energy in the form of ATP (adenosine triphosphate). Specifically, pyruvate kinase catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), resulting in the formation of pyruvate and ATP.

There are several isoforms of pyruvate kinase found in different tissues, including the liver, muscle, and brain. The type found in red blood cells is known as PK-RBC or PK-M2. Deficiencies in pyruvate kinase can lead to a genetic disorder called pyruvate kinase deficiency, which can result in hemolytic anemia due to the premature destruction of red blood cells.

Mitogen-Activated Protein Kinase 1 (MAPK1), also known as Extracellular Signal-Regulated Kinase 2 (ERK2), is a protein kinase that plays a crucial role in intracellular signal transduction pathways. It is a member of the MAPK family, which regulates various cellular processes such as proliferation, differentiation, apoptosis, and stress response.

MAPK1 is activated by a cascade of phosphorylation events initiated by upstream activators like MAPKK (Mitogen-Activated Protein Kinase Kinase) in response to various extracellular signals such as growth factors, hormones, and mitogens. Once activated, MAPK1 phosphorylates downstream targets, including transcription factors and other protein kinases, thereby modulating their activities and ultimately influencing gene expression and cellular responses.

MAPK1 is widely expressed in various tissues and cells, and its dysregulation has been implicated in several pathological conditions, including cancer, inflammation, and neurodegenerative diseases. Therefore, understanding the regulation and function of MAPK1 signaling pathways has important implications for developing therapeutic strategies to treat these disorders.

Calcium channels are specialized proteins that span the membrane of cells and allow calcium ions (Ca²+) to flow in and out of the cell. They are crucial for many physiological processes, including muscle contraction, neurotransmitter release, hormone secretion, and gene expression.

There are several types of calcium channels, classified based on their biophysical and pharmacological properties. The most well-known are:

1. Voltage-gated calcium channels (VGCCs): These channels are activated by changes in the membrane potential. They are further divided into several subtypes, including L-type, P/Q-type, N-type, R-type, and T-type. VGCCs play a critical role in excitation-contraction coupling in muscle cells and neurotransmitter release in neurons.
2. Receptor-operated calcium channels (ROCCs): These channels are activated by the binding of an extracellular ligand, such as a hormone or neurotransmitter, to a specific receptor on the cell surface. ROCCs are involved in various physiological processes, including smooth muscle contraction and platelet activation.
3. Store-operated calcium channels (SOCCs): These channels are activated by the depletion of intracellular calcium stores, such as those found in the endoplasmic reticulum. SOCCs play a critical role in maintaining calcium homeostasis and signaling within cells.

Dysregulation of calcium channel function has been implicated in various diseases, including hypertension, arrhythmias, migraine, epilepsy, and neurodegenerative disorders. Therefore, calcium channels are an important target for drug development and therapy.

Death-associated protein kinases (DAPKs) are a group of serine/threonine protein kinases that have been implicated in the regulation of programmed cell death, also known as apoptosis. There are several isoforms of DAPKs, including DAPK1, DAPK2, and DAPK3, each with distinct functions and regulatory mechanisms.

DAPK1 was the first to be identified and is perhaps the best studied. It plays a critical role in various forms of programmed cell death, including apoptosis, autophagy, and necroptosis. DAPK1 can be activated by various stimuli, such as calcium influx, oxidative stress, and DNA damage, and its activation leads to the phosphorylation of several downstream targets that contribute to the execution of cell death.

DAPK2 and DAPK3 have also been shown to regulate programmed cell death, although their functions are less well understood than those of DAPK1. DAPK2 has been implicated in the regulation of autophagy, while DAPK3 has been suggested to play a role in the regulation of both apoptosis and necroptosis.

Overall, DAPKs are important regulators of programmed cell death and have been implicated in various physiological and pathological processes, including development, neurodegeneration, ischemia-reperfusion injury, and cancer.

Cyclic AMP (cAMP)-dependent protein kinase catalytic subunits, also known as protein kinase A (PKA) catalytic subunits, are key enzymes that play a crucial role in intracellular signaling pathways. These subunits are responsible for the regulation of various cellular processes, including metabolism, gene expression, and cell growth and differentiation.

The activation of cAMP-dependent protein kinase catalytic subunits occurs through a cascade of events that begins with the binding of extracellular signals to G protein-coupled receptors (GPCRs) on the cell surface. This binding event activates adenylyl cyclase, an enzyme that converts ATP to cAMP. The increased levels of cAMP then bind to and activate regulatory subunits of cAMP-dependent protein kinase, leading to the release and activation of the catalytic subunits.

Once activated, the cAMP-dependent protein kinase catalytic subunits phosphorylate specific serine and threonine residues on target proteins, thereby modulating their activity and function. This process is reversible, as phosphatases can dephosphorylate these residues and inactivate the target proteins.

There are four different isoforms of cAMP-dependent protein kinase catalytic subunits (PKA-Cα, PKA-Cβ, PKA-Cγ, and PKA-Cδ) that are encoded by separate genes but share a high degree of sequence homology. These isoforms can form homodimers or heterodimers with each other, and their expression patterns and subcellular localization can vary depending on the cell type and physiological context.

Overall, cAMP-dependent protein kinase catalytic subunits are essential regulators of many fundamental cellular processes, and their dysregulation has been implicated in various diseases, including cancer, diabetes, and neurological disorders.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Sequence homology, amino acid, refers to the similarity in the order of amino acids in a protein or a portion of a protein between two or more species. This similarity can be used to infer evolutionary relationships and functional similarities between proteins. The higher the degree of sequence homology, the more likely it is that the proteins are related and have similar functions. Sequence homology can be determined through various methods such as pairwise alignment or multiple sequence alignment, which compare the sequences and calculate a score based on the number and type of matching amino acids.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

Mycelium is not a specifically medical term, but it is a biological term used in fungi and other organisms. Medically, it might be relevant in certain contexts such as discussing fungal infections. Here's the general definition:

Mycelium (my-SEE-lee-um) is the vegetative part of a fungus, consisting of a mass of branching, thread-like hyphae. It is the underground portion of the fungus that supports the growth of the organism and is often responsible for the decomposition of organic material. Mycelium can be found in various environments, including soil, water, and dead or living organisms.

Phosphoprotein phosphatases (PPPs) are a family of enzymes that play a crucial role in the regulation of various cellular processes by removing phosphate groups from serine, threonine, and tyrosine residues on proteins. Phosphorylation is a post-translational modification that regulates protein function, localization, and stability, and dephosphorylation by PPPs is essential for maintaining the balance of this regulation.

The PPP family includes several subfamilies, such as PP1, PP2A, PP2B (also known as calcineurin), PP4, PP5, and PP6. Each subfamily has distinct substrate specificities and regulatory mechanisms. For example, PP1 and PP2A are involved in the regulation of metabolism, signal transduction, and cell cycle progression, while PP2B is involved in immune response and calcium signaling.

Dysregulation of PPPs has been implicated in various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. Therefore, understanding the function and regulation of PPPs is important for developing therapeutic strategies to target these diseases.

Mitogen-Activated Protein Kinase Kinases (MAP2K or MEK) are a group of protein kinases that play a crucial role in intracellular signal transduction pathways. They are so named because they are activated by mitogens, which are substances that stimulate cell division, and other extracellular signals.

MAP2Ks are positioned upstream of the Mitogen-Activated Protein Kinases (MAPK) in a three-tiered kinase cascade. Once activated, MAP2Ks phosphorylate and activate MAPKs, which then go on to regulate various cellular processes such as proliferation, differentiation, survival, and apoptosis.

There are several subfamilies of MAP2Ks, including MEK1/2, MEK3/6 (also known as MKK3/6), MEK4/7 (also known as MKK4/7), and MEK5. Each MAP2K is specific to activating a particular MAPK, and they are activated by different MAP3Ks (MAP kinase kinase kinases) in response to various extracellular signals.

Dysregulation of the MAPK/MAP2K signaling pathways has been implicated in numerous diseases, including cancer, cardiovascular disease, and neurological disorders. Therefore, targeting these pathways with therapeutic agents has emerged as a promising strategy for treating various diseases.

Mitogen-Activated Protein Kinase 3 (MAPK3), also known as extracellular signal-regulated kinase 1 (ERK1), is a serine/threonine protein kinase that plays a crucial role in intracellular signal transduction pathways. It is involved in the regulation of various cellular processes, including proliferation, differentiation, and survival, in response to extracellular stimuli such as growth factors, hormones, and stress.

MAPK3 is activated through a phosphorylation cascade that involves the activation of upstream MAPK kinases (MKK or MEK). Once activated, MAPK3 can phosphorylate and activate various downstream targets, including transcription factors, to regulate gene expression. Dysregulation of MAPK3 signaling has been implicated in several diseases, including cancer and neurological disorders.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Protein Kinase C-delta (PKC-δ) is a specific isoform of the Protein Kinase C (PKC) family, which are serine/threonine protein kinases that play crucial roles in various cellular signaling pathways. PKC-δ is involved in several cellular processes such as proliferation, differentiation, apoptosis, and motility. It is activated by second messengers like diacylglycerol (DAG) and calcium ions (Ca2+), and its activation leads to the phosphorylation of specific target proteins, thereby modulating their functions. Aberrant regulation of PKC-δ has been implicated in various diseases, including cancer and neurodegenerative disorders.

Isoquinolines are not a medical term per se, but a chemical classification. They refer to a class of organic compounds that consist of a benzene ring fused to a piperidine ring. This structure is similar to that of quinoline, but with the nitrogen atom located at a different position in the ring.

Isoquinolines have various biological activities and can be found in some natural products, including certain alkaloids. Some isoquinoline derivatives have been developed as drugs for the treatment of various conditions, such as cardiovascular diseases, neurological disorders, and cancer. However, specific medical definitions related to isoquinolines typically refer to the use or effects of these specific drugs rather than the broader class of compounds.

Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.

JNK (c-Jun N-terminal kinase) Mitogen-Activated Protein Kinases are a subgroup of the Ser/Thr protein kinases that are activated by stress stimuli and play important roles in various cellular processes, including inflammation, apoptosis, and differentiation. They are involved in the regulation of gene expression through phosphorylation of transcription factors such as c-Jun. JNKs are activated by a variety of upstream kinases, including MAP2Ks (MKK4/SEK1 and MKK7), which are in turn activated by MAP3Ks (such as ASK1, MEKK1, MLKs, and TAK1). JNK signaling pathways have been implicated in various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases.

I'm sorry for any confusion, but "Peptide T" is not a widely recognized or established medical term. It appears that you might be referring to "T-20," which is also known as "Enfuvirtide." Enfuvirtide is a medication used in the treatment of HIV infection. It is a synthetic peptide that mimics a portion of the gp41 protein, which is a component of the viral envelope of HIV. By binding to this protein, enfuvirtide prevents the virus from infecting cells, providing an additional line of defense against the virus in combination therapy regimens.

If you meant something else by "Peptide T," please provide more context or clarify your question so I can give you a more accurate answer.

Serine is an amino acid, which is a building block of proteins. More specifically, it is a non-essential amino acid, meaning that the body can produce it from other compounds, and it does not need to be obtained through diet. Serine plays important roles in the body, such as contributing to the formation of the protective covering of nerve fibers (myelin sheath), helping to synthesize another amino acid called tryptophan, and taking part in the metabolism of fatty acids. It is also involved in the production of muscle tissues, the immune system, and the forming of cell structures. Serine can be found in various foods such as soy, eggs, cheese, meat, peanuts, lentils, and many others.

Phosphoproteins are proteins that have been post-translationally modified by the addition of a phosphate group (-PO3H2) onto specific amino acid residues, most commonly serine, threonine, or tyrosine. This process is known as phosphorylation and is mediated by enzymes called kinases. Phosphoproteins play crucial roles in various cellular processes such as signal transduction, cell cycle regulation, metabolism, and gene expression. The addition or removal of a phosphate group can activate or inhibit the function of a protein, thereby serving as a switch to control its activity. Phosphoproteins can be detected and quantified using techniques such as Western blotting, mass spectrometry, and immunofluorescence.

Cyclic nucleotides are formed by the intramolecular phosphoester bond between the phosphate group and the hydroxyl group at the 3'-carbon atom of the ribose sugar in a nucleotide. This creates a cyclic structure, specifically a cyclic phosphate. The most common cyclic nucleotides are cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These molecules function as second messengers in cells, playing crucial roles in various cellular signaling pathways related to metabolism, gene expression, and cell differentiation. The levels of cAMP and cGMP are tightly regulated by the activities of enzymes such as adenylate cyclase and guanylate cyclase for their synthesis, and phosphodiesterases for their degradation.

I apologize, but I am not able to provide a medical definition for "Egtazic Acid" because it is not a term that is recognized in the field of medicine or pharmacology. It is possible that you may have meant "Egтарic Acid," which also does not have a specific medical meaning, or "Ethylene Glycol Tetraacetic Acid (EGTA)," which is a chemical compound used in research and medicine for its ability to bind calcium ions. If you have any other questions, I would be happy to try to help answer them.

Molecular weight, also known as molecular mass, is the mass of a molecule. It is expressed in units of atomic mass units (amu) or daltons (Da). Molecular weight is calculated by adding up the atomic weights of each atom in a molecule. It is a useful property in chemistry and biology, as it can be used to determine the concentration of a substance in a solution, or to calculate the amount of a substance that will react with another in a chemical reaction.

AMP-activated protein kinases (AMPK) are a group of heterotrimeric enzymes that play a crucial role in cellular energy homeostasis. They are composed of a catalytic subunit (α) and two regulatory subunits (β and γ). AMPK is activated under conditions of low energy charge, such as ATP depletion, hypoxia, or exercise, through an increase in the AMP:ATP ratio.

Once activated, AMPK phosphorylates and regulates various downstream targets involved in metabolic pathways, including glycolysis, fatty acid oxidation, and protein synthesis. This results in the inhibition of energy-consuming processes and the promotion of energy-producing processes, ultimately helping to restore cellular energy balance.

AMPK has been implicated in a variety of physiological processes, including glucose and lipid metabolism, autophagy, mitochondrial biogenesis, and inflammation. Dysregulation of AMPK activity has been linked to several diseases, such as diabetes, obesity, cancer, and neurodegenerative disorders. Therefore, AMPK is an attractive target for therapeutic interventions in these conditions.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

I believe there may be some confusion in your question. "Rabbits" is a common name used to refer to the Lagomorpha species, particularly members of the family Leporidae. They are small mammals known for their long ears, strong legs, and quick reproduction.

However, if you're referring to "rabbits" in a medical context, there is a term called "rabbit syndrome," which is a rare movement disorder characterized by repetitive, involuntary movements of the fingers, resembling those of a rabbit chewing. It is also known as "finger-chewing chorea." This condition is usually associated with certain medications, particularly antipsychotics, and typically resolves when the medication is stopped or adjusted.

Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.

I'm sorry for any confusion, but "Protamine Kinase" is not a widely recognized or established term in medical or biological sciences. Protamines are small, arginine-rich proteins found in the sperm cells of many organisms, and they play a crucial role in the packaging and protection of DNA during spermatogenesis.

Kinases, on the other hand, are enzymes that catalyze the transfer of phosphate groups from ATP to specific amino acids in proteins, thereby modulating their function, localization, or stability.

A search of scientific literature reveals only a few instances where "protamine kinase" is mentioned, usually in the context of potential regulatory mechanisms during sperm maturation or fertilization. However, there is no widely accepted or well-characterized enzyme known as "protamine kinase." Therefore, it would be challenging to provide a concise and accurate medical definition for this term.

Cytosol refers to the liquid portion of the cytoplasm found within a eukaryotic cell, excluding the organelles and structures suspended in it. It is the site of various metabolic activities and contains a variety of ions, small molecules, and enzymes. The cytosol is where many biochemical reactions take place, including glycolysis, protein synthesis, and the regulation of cellular pH. It is also where some organelles, such as ribosomes and vesicles, are located. In contrast to the cytosol, the term "cytoplasm" refers to the entire contents of a cell, including both the cytosol and the organelles suspended within it.

Recombinant fusion proteins are artificially created biomolecules that combine the functional domains or properties of two or more different proteins into a single protein entity. They are generated through recombinant DNA technology, where the genes encoding the desired protein domains are linked together and expressed as a single, chimeric gene in a host organism, such as bacteria, yeast, or mammalian cells.

The resulting fusion protein retains the functional properties of its individual constituent proteins, allowing for novel applications in research, diagnostics, and therapeutics. For instance, recombinant fusion proteins can be designed to enhance protein stability, solubility, or immunogenicity, making them valuable tools for studying protein-protein interactions, developing targeted therapies, or generating vaccines against infectious diseases or cancer.

Examples of recombinant fusion proteins include:

1. Etaglunatide (ABT-523): A soluble Fc fusion protein that combines the heavy chain fragment crystallizable region (Fc) of an immunoglobulin with the extracellular domain of the human interleukin-6 receptor (IL-6R). This fusion protein functions as a decoy receptor, neutralizing IL-6 and its downstream signaling pathways in rheumatoid arthritis.
2. Etanercept (Enbrel): A soluble TNF receptor p75 Fc fusion protein that binds to tumor necrosis factor-alpha (TNF-α) and inhibits its proinflammatory activity, making it a valuable therapeutic option for treating autoimmune diseases like rheumatoid arthritis, ankylosing spondylitis, and psoriasis.
3. Abatacept (Orencia): A fusion protein consisting of the extracellular domain of cytotoxic T-lymphocyte antigen 4 (CTLA-4) linked to the Fc region of an immunoglobulin, which downregulates T-cell activation and proliferation in autoimmune diseases like rheumatoid arthritis.
4. Belimumab (Benlysta): A monoclonal antibody that targets B-lymphocyte stimulator (BLyS) protein, preventing its interaction with the B-cell surface receptor and inhibiting B-cell activation in systemic lupus erythematosus (SLE).
5. Romiplostim (Nplate): A fusion protein consisting of a thrombopoietin receptor agonist peptide linked to an immunoglobulin Fc region, which stimulates platelet production in patients with chronic immune thrombocytopenia (ITP).
6. Darbepoetin alfa (Aranesp): A hyperglycosylated erythropoiesis-stimulating protein that functions as a longer-acting form of recombinant human erythropoietin, used to treat anemia in patients with chronic kidney disease or cancer.
7. Palivizumab (Synagis): A monoclonal antibody directed against the F protein of respiratory syncytial virus (RSV), which prevents RSV infection and is administered prophylactically to high-risk infants during the RSV season.
8. Ranibizumab (Lucentis): A recombinant humanized monoclonal antibody fragment that binds and inhibits vascular endothelial growth factor A (VEGF-A), used in the treatment of age-related macular degeneration, diabetic retinopathy, and other ocular disorders.
9. Cetuximab (Erbitux): A chimeric monoclonal antibody that binds to epidermal growth factor receptor (EGFR), used in the treatment of colorectal cancer and head and neck squamous cell carcinoma.
10. Adalimumab (Humira): A fully humanized monoclonal antibody that targets tumor necrosis factor-alpha (TNF-α), used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriasis, and Crohn's disease.
11. Bevacizumab (Avastin): A recombinant humanized monoclonal antibody that binds to VEGF-A, used in the treatment of various cancers, including colorectal, lung, breast, and kidney cancer.
12. Trastuzumab (Herceptin): A humanized monoclonal antibody that targets HER2/neu receptor, used in the treatment of breast cancer.
13. Rituximab (Rituxan): A chimeric monoclonal antibody that binds to CD20 antigen on B cells, used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis.
14. Palivizumab (Synagis): A humanized monoclonal antibody that binds to the F protein of respiratory syncytial virus, used in the prevention of respiratory syncytial virus infection in high-risk infants.
15. Infliximab (Remicade): A chimeric monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis.
16. Natalizumab (Tysabri): A humanized monoclonal antibody that binds to α4β1 integrin, used in the treatment of multiple sclerosis and Crohn's disease.
17. Adalimumab (Humira): A fully human monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, and ulcerative colitis.
18. Golimumab (Simponi): A fully human monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.
19. Certolizumab pegol (Cimzia): A PEGylated Fab' fragment of a humanized monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease.
20. Ustekinumab (Stelara): A fully human monoclonal antibody that targets IL-12 and IL-23, used in the treatment of psoriasis, psoriatic arthritis, and Crohn's disease.
21. Secukinumab (Cosentyx): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis.
22. Ixekizumab (Taltz): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis and psoriatic arthritis.
23. Brodalumab (Siliq): A fully human monoclonal antibody that targets IL-17 receptor A, used in the treatment of psoriasis.
24. Sarilumab (Kevzara): A fully human monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis.
25. Tocilizumab (Actemra): A humanized monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, and chimeric antigen receptor T-cell-induced cytokine release syndrome.
26. Siltuximab (Sylvant): A chimeric monoclonal antibody that targets IL-6, used in the treatment of multicentric Castleman disease.
27. Satralizumab (Enspryng): A humanized monoclonal antibody that targets IL-6 receptor alpha, used in the treatment of neuromyelitis optica spectrum disorder.
28. Sirukumab (Plivensia): A human monoclonal antibody that targets IL-6, used in the treatment

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Dietary calcium is a type of calcium that is obtained through food sources. Calcium is an essential mineral that is necessary for many bodily functions, including bone formation and maintenance, muscle contraction, nerve impulse transmission, and blood clotting.

The recommended daily intake of dietary calcium varies depending on age, sex, and other factors. For example, the recommended daily intake for adults aged 19-50 is 1000 mg, while women over 50 and men over 70 require 1200 mg per day.

Good dietary sources of calcium include dairy products such as milk, cheese, and yogurt; leafy green vegetables like broccoli and kale; fortified cereals and juices; and certain types of fish, such as salmon and sardines. It is important to note that some foods can inhibit the absorption of calcium, including oxalates found in spinach and rhubarb, and phytates found in whole grains and legumes.

If a person is unable to get enough calcium through their diet, they may need to take calcium supplements. However, it is important to talk to a healthcare provider before starting any new supplement regimen, as excessive intake of calcium can lead to negative health effects.

SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases that play important roles in various cellular processes, including cell proliferation, differentiation, survival, and migration. They are named after the founding member, SRC, which was first identified as an oncogene in Rous sarcoma virus.

SFKs share a common structure, consisting of an N-terminal unique domain, a SH3 domain, a SH2 domain, a catalytic kinase domain, and a C-terminal regulatory tail with a negative regulatory tyrosine residue (Y527 in human SRC). In their inactive state, SFKs are maintained in a closed conformation through intramolecular interactions between the SH3 domain, SH2 domain, and the phosphorylated C-terminal tyrosine.

Upon activation by various signals, such as growth factors, cytokines, or integrin engagement, SFKs are activated through a series of events that involve dephosphorylation of the regulatory tyrosine residue, recruitment to membrane receptors via their SH2 and SH3 domains, and trans-autophosphorylation of the activation loop in the kinase domain.

Once activated, SFKs can phosphorylate a wide range of downstream substrates, including other protein kinases, adaptor proteins, and cytoskeletal components, thereby regulating various signaling pathways that control cell behavior. Dysregulation of SFK activity has been implicated in various diseases, including cancer, inflammation, and neurological disorders.

The hippocampus is a complex, curved formation in the brain that resembles a seahorse (hence its name, from the Greek word "hippos" meaning horse and "kampos" meaning sea monster). It's part of the limbic system and plays crucial roles in the formation of memories, particularly long-term ones.

This region is involved in spatial navigation and cognitive maps, allowing us to recognize locations and remember how to get to them. Additionally, it's one of the first areas affected by Alzheimer's disease, which often results in memory loss as an early symptom.

Anatomically, it consists of two main parts: the Ammon's horn (or cornu ammonis) and the dentate gyrus. These structures are made up of distinct types of neurons that contribute to different aspects of learning and memory.

Protein Kinase C-epsilon (PKCε) is a serine-threonine protein kinase that belongs to the family of Protein Kinase C (PKC) enzymes. These enzymes play crucial roles in various cellular processes, including signal transduction, cell survival, differentiation, and apoptosis.

PKCε is specifically involved in regulating several signaling pathways related to inflammation, proliferation, and carcinogenesis. It can be activated by different stimuli such as diacylglycerol (DAG) and phorbol esters, which lead to its translocation from the cytosol to the plasma membrane, where it phosphorylates and modulates the activity of various target proteins.

Abnormal regulation or expression of PKCε has been implicated in several diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. Therefore, PKCε is considered a potential therapeutic target for these conditions, and inhibitors of this enzyme are being developed and tested in preclinical and clinical studies.

Electrophoresis, polyacrylamide gel (EPG) is a laboratory technique used to separate and analyze complex mixtures of proteins or nucleic acids (DNA or RNA) based on their size and electrical charge. This technique utilizes a matrix made of cross-linked polyacrylamide, a type of gel, which provides a stable and uniform environment for the separation of molecules.

In this process:

1. The polyacrylamide gel is prepared by mixing acrylamide monomers with a cross-linking agent (bis-acrylamide) and a catalyst (ammonium persulfate) in the presence of a buffer solution.
2. The gel is then poured into a mold and allowed to polymerize, forming a solid matrix with uniform pore sizes that depend on the concentration of acrylamide used. Higher concentrations result in smaller pores, providing better resolution for separating smaller molecules.
3. Once the gel has set, it is placed in an electrophoresis apparatus containing a buffer solution. Samples containing the mixture of proteins or nucleic acids are loaded into wells on the top of the gel.
4. An electric field is applied across the gel, causing the negatively charged molecules to migrate towards the positive electrode (anode) while positively charged molecules move toward the negative electrode (cathode). The rate of migration depends on the size, charge, and shape of the molecules.
5. Smaller molecules move faster through the gel matrix and will migrate farther from the origin compared to larger molecules, resulting in separation based on size. Proteins and nucleic acids can be selectively stained after electrophoresis to visualize the separated bands.

EPG is widely used in various research fields, including molecular biology, genetics, proteomics, and forensic science, for applications such as protein characterization, DNA fragment analysis, cloning, mutation detection, and quality control of nucleic acid or protein samples.

Protein Kinase C beta (PKCβ) is a serine-threonine protein kinase that belongs to the family of Protein Kinase C (PKC) enzymes. It plays a crucial role in various cellular processes, including signal transduction, cell survival, differentiation, and apoptosis. PKCβ is activated by diacylglycerol (DAG) and calcium ions (Ca2+), which results in its translocation from the cytosol to the plasma membrane, where it phosphorylates downstream target proteins.

There are two isoforms of PKCβ, PKCβI and PKCβII, which differ in their regulatory domains but have similar catalytic domains. PKCβ has been implicated in several diseases, including cancer, diabetes, and inflammatory disorders, making it a potential therapeutic target for drug development.

Protein-Tyrosine Kinases (PTKs) are a type of enzyme that plays a crucial role in various cellular functions, including signal transduction, cell growth, differentiation, and metabolism. They catalyze the transfer of a phosphate group from ATP to the tyrosine residues of proteins, thereby modifying their activity, localization, or interaction with other molecules.

PTKs can be divided into two main categories: receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs are transmembrane proteins that become activated upon binding to specific ligands, such as growth factors or hormones. NRTKs, on the other hand, are intracellular enzymes that can be activated by various signals, including receptor-mediated signaling and intracellular messengers.

Dysregulation of PTK activity has been implicated in several diseases, such as cancer, diabetes, and inflammatory disorders. Therefore, PTKs are important targets for drug development and therapy.

Biological models, also known as physiological models or organismal models, are simplified representations of biological systems, processes, or mechanisms that are used to understand and explain the underlying principles and relationships. These models can be theoretical (conceptual or mathematical) or physical (such as anatomical models, cell cultures, or animal models). They are widely used in biomedical research to study various phenomena, including disease pathophysiology, drug action, and therapeutic interventions.

Examples of biological models include:

1. Mathematical models: These use mathematical equations and formulas to describe complex biological systems or processes, such as population dynamics, metabolic pathways, or gene regulation networks. They can help predict the behavior of these systems under different conditions and test hypotheses about their underlying mechanisms.
2. Cell cultures: These are collections of cells grown in a controlled environment, typically in a laboratory dish or flask. They can be used to study cellular processes, such as signal transduction, gene expression, or metabolism, and to test the effects of drugs or other treatments on these processes.
3. Animal models: These are living organisms, usually vertebrates like mice, rats, or non-human primates, that are used to study various aspects of human biology and disease. They can provide valuable insights into the pathophysiology of diseases, the mechanisms of drug action, and the safety and efficacy of new therapies.
4. Anatomical models: These are physical representations of biological structures or systems, such as plastic models of organs or tissues, that can be used for educational purposes or to plan surgical procedures. They can also serve as a basis for developing more sophisticated models, such as computer simulations or 3D-printed replicas.

Overall, biological models play a crucial role in advancing our understanding of biology and medicine, helping to identify new targets for therapeutic intervention, develop novel drugs and treatments, and improve human health.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

1-Phosphatidylinositol 4-Kinase (PI4K) is a type of enzyme that belongs to the family of kinases, which are enzymes that transfer phosphate groups from high-energy donor molecules to specific target proteins or lipids in the cell. PI4K specifically phosphorylates the 4th position on the inositol ring of phosphatidylinositol (PI), a type of phospholipid found in the cell membrane, converting it to phosphatidylinositol 4-phosphate (PI4P).

PI4K has several isoforms, including PI4K alpha, beta, gamma, and delta, which are located in different cellular compartments and play distinct roles. For example, PI4K alpha and beta are primarily involved in vesicle trafficking and Golgi function, while PI4K gamma and delta are associated with the plasma membrane and regulate ion channels and other signaling pathways.

PI4P, the product of PI4K activity, is an important signaling molecule that regulates various cellular processes, including membrane trafficking, cytoskeleton organization, and protein sorting. Dysregulation of PI4K and its downstream pathways has been implicated in several human diseases, such as cancer, neurodegeneration, and viral infection.

"CAMK2A calcium/calmodulin dependent protein kinase II alpha [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. ... β CAMKIIδ CAMKIIγ CAMKIII CAMKIV CAMKV CaM kinase like vesicle associated SCAMK Ca2+/calmodulin-dependent protein kinase kinase ... CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. ... Hudmon A, Schulman H (2002-06-01). "Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and ...
... interleukin-1 receptor accessory protein-like 1 protein) PI4KIIIβ (type III phosphatidylinositol 4-kinase β) IP3 receptor (this ... PIK1 It binds to many proteins, some in calcium dependent and some in calcium independent ways, and switches many of the ... calcium-binding protein. Frq can substitute for calmodulin in some situations. It is thought to be associated with neuronal ... NCS-1 is a member of the neuronal calcium sensor family, a class of EF hand containing calcium-myristoyl-switch proteins. NCS-1 ...
... p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent ... Sakashita G, Shima H, Komatsu M, Urano T, Kikuchi A, Kikuchi K (February 2003). "Regulation of type 1 protein phosphatase/ ... p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent ... Agarwal-Mawal A, Paudel HK (June 2001). "Neuronal Cdc2-like protein kinase (Cdk5/p25) is associated with protein phosphatase 1 ...
Ca2+/calmodulin-dependent protein kinase II (CaMK II) is also activated by calcium influx through NMDA receptors, and is ... Lacosamide is used in combination with other types of medications to control various types of seizures, especially epilepsy. ... and cyclin-dependent protein kinase 5 (Cdk5) are highly expressed in Alzheimer's disease and are some of the protein kinases ... revealing the presence of both Rho kinase-dependent and Rho kinase-independent pathways for the growth cone collapse. In RhoA ...
CAMK2G and CAMK2D belong to the same calcium/calmodulin dependent protein kinase subfamily. These kinases play important roles ... Namely apoptosis of type 2 alveolar epithelial cell (L2) through the AMPK-regulated endoplasmic reticulum (ER) stress-triggered ... Including the activation of ERK and other mitogen-activated protein kinases. eNOS or endothelial nitric oxide synthase ... Mifflin, L.; Ofengeim, D.; Yuan, J. (2020). "Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target". Nature ...
... neural protein contains phosphorylation sites for cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase ... Lack of synapsins altogether in neurons, leads to behavioral alterations as well as epileptic-type seizures. The lack affects ... and domain B has two mitogen-activated protein kinase phosphorylation sites. At its B domain, between amino acids 43 and 121, ... The synapsin II protein has been shown to interact with SYN1. Mutations in the SYN2 gene may be associated with abnormal ...
... calcium/calmodulin-dependent serine protein kinase 3 and membrane-associated guanylate kinase 2. CASK gene mutations are the ... Hsueh YP, Roberts AM, Volta M, Sheng M, Roberts RG (June 2001). "Bipartite interaction between neurofibromatosis type I protein ... "Entrez Gene: CASK Calcium/calmodulin-dependent serine protein kinase (MAGUK family)". Tarpey PS, Smith R, Pleasance E, Whibley ... Zhu ZQ, Wang D, Xiang D, Yuan YX, Wang Y (January 2014). "Calcium/calmodulin-dependent serine protein kinase is involved in ...
Zhang S, Ehlers MD, Bernhardt JP, Su CT, Huganir RL (August 1998). "Calmodulin mediates calcium-dependent inactivation of N- ... ". "Protein Information - Basic Information: Protein COPaKB ID: P35609". Cardiac Organellar Protein Atlas Knowledgebase. ... Young P, Ferguson C, Bañuelos S, Gautel M (March 1998). "Molecular structure of the sarcomeric Z-disk: two types of titin ... "Interactions of calmodulin and alpha-actinin with the NR1 subunit modulate Ca2+-dependent inactivation of NMDA receptors". The ...
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene. The product of ... calmodulin-dependent protein kinase I by calmodulin and by Ca2+/calmodulin-dependent protein kinase kinase". J. Biol. Chem. 273 ... Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification ... and activation of Ca2+-calmodulin-dependent protein kinase IV by Ca2+-calmodulin-dependent protein kinase Ia kinase. ...
Calcium/calmodulin-dependent protein kinase type 1 - Homo sapiens (Human) - CAMK1 gene & protein". www.uniprot.org. Retrieved ... calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine ... July 2005). "Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase ... and to the Ca++/calmodulin-dependent protein kinase subfamily. This protein plays a role in the calcium/calmodulin-dependent ( ...
... by protein kinase C and calcium/calmodulin kinase II in vitro". J. Neurochem. 71 (3): 1307-14. doi:10.1046/j.1471-4159.1998. ... Kubes M, Cordier J, Glowinski J, Girault JA, Chneiweiss H (1998). "Endothelin induces a calcium-dependent phosphorylation of ... "Molecular characterization of the human PEA15 gene on 1q21-q22 and association with type 2 diabetes mellitus in Pima Indians". ... "Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action". Mol. Cell. Biol. 23 (13): 4511 ...
... suggesting that inhibition of Ca2+/calmodulin-dependent protein kinase II may also be a potential treatment strategy. These ... which can be explained by decreased voltage-dependent calcium channel expression, specifically Ca(v)1.3, which is responsible ... Initially, a Glu1425Gly mutation in ANK2 was found to cause dominantly-inherited long QT syndrome type 4, cardiac arrhythmia. ... Effects on ryanodine receptors specifically were also rescued by a potent Ca2+/calmodulin-dependent protein kinase II inhibitor ...
... p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent ... Alpha-actinin-1 has been shown to interact with: CDK5R1, CDK5R2, Collagen, type XVII, alpha 1, GIPC1, PDLIM1, Protein kinase N1 ... Alpha-actinin-1 is an F-actin cross-linking protein - a bundling protein that is thought to anchor actin to a number of ... Bunn RC, Jensen MA, Reed BC (1999). "Protein interactions with the glucose transporter binding protein GLUT1CBP that provide a ...
... encoding enzyme Pyridoxal kinase PFKL: encoding enzyme ATP-dependent 6-phosphofructokinase, liver type PIGP: encoding ... encoding protein RWD domain-containing protein 2B S100B: encoding calcium binding protein SAMSN1: encoding SAM domain- ... binding protein 3 PCNT: encoding protein centrosomal pericentrin PCP4: encoding calmodulin regulator protein PCP4 PDE9A: ... a C-type lectin CLDN8: encoding protein claudin-8 CLDN14: encoding protein claudin-14 CLDN17: encoding protein claudin-17 CLIC6 ...
The δ subunit is the ubiquitous eukaryotic protein calmodulin which itself has 4 calcium ion binding sites. When cytosolic Ca2+ ... but phosphorylation of both these subunits by protein kinase A (PKA, or cAMP-dependent protein kinase) reduces their respective ... Defects in phosphorylase kinase genes are the cause of glycogen storage disease type IX (GSD type IX) and GSD type VI (formerly ... In the active site, there is significant homology between PhK and other so-called P-loop protein kinases such as protein kinase ...
Calcium/calmodulin-dependent protein kinase type II gamma chain is an enzyme that in humans is encoded by the CAMK2G gene. The ... "Entrez Gene: CAMK2G calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma". Moyers JS, Bilan PJ, Zhu J, Kahn CR ( ... Calcium/calmodulin-dependent protein kinase type II subunit gamma) at the PDBe-KB. Portal: Biology This article incorporates ... calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic ...
Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in a type of synaptic plasticity known as long-term ... Many of the proteins that calmodulin binds are unable to bind calcium themselves, and use calmodulin as a calcium sensor and ... Proteopedia page for Calmodulin and its conformational change Protein kinase Ca2+/calmodulin-dependent protein kinase Stevens ... This MLC kinase is activated by a calmodulin when it is bound by calcium, thus making smooth muscle contraction dependent on ...
Calcium/calmodulin-dependent protein kinase type II beta chain is an enzyme that in humans is encoded by the CAMK2B gene. The ... "Entrez Gene: CAMK2B calcium/calmodulin-dependent protein kinase (CaM kinase) II beta". Walikonis RS, Oguni A, Khorosheva EM, ... Sequence analyses of human brain calcium/calmodulin-dependent protein kinase II". Mol. Biol. Rep. 28 (1): 35-41. doi:10.1023/A: ... Novak G, Seeman P, Tallerico T (2001). "Schizophrenia: elevated mRNA for calcium-calmodulin-dependent protein kinase IIbeta in ...
... an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent ... calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5. Figure 2 ... ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high-fat food, ... it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting ...
... and a calcium/calmodulin-dependent kinase (CAMK-1), and additional kinases, reaching its peak around mid-subjective day. Kinase ... with just one of the proteins present. The choice of which protein is made is the result of temperature-dependent splicing of ... Because sFRQ favors a longer period than lFRQ, free running rhythms in wild type Neurospora are somewhat decreased with ... A similar palette of kinases modifies the clock proteins in all cases. Negative feedback White Collar-1 Baker CL, Loros JJ, ...
This calcium then interacts with calcineurin and calcium/calmodulin-dependent kinases that in turn activate transcription ... October 2004). "Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes". Science. 306 (5695): 457-61. ... "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1". Science. 287 (5453): ... PERK (protein kinase RNA-like endoplasmic reticulum kinase) activates itself by oligomerization and autophosphorylation of the ...
... the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase ... "The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments". ... S100 calcium-binding protein B (S100B) is a protein of the S-100 protein family. S100 proteins are localized in the cytoplasm ... the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase ...
Cannabinoids reduce calcium influx by blocking the activity of voltage-dependent N-, P/Q- and L-type calcium channels. In ... through Gi/o-mediated inhibition of adenylyl cyclase and protein kinase A. Direct effects of CB1 receptors on membrane ... decreases in expression were seen in both calmodulin and ribosomal RNAs. In addition, CB1 activation has been demonstrated to ... Guo J, Ikeda SR (2004). "Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium ...
"Calmodulin is involved in the Ca2+-dependent activation of ceramide kinase as a calcium sensor". J. Biol. Chem. 280 (49): 40436 ... CERK shares sequence homology with sphingosine kinase type I, including an N-terminal pleckstrin homology (PH) domain and a ... It was demonstrated that C-1-P perpetuates the phosphorylation of glycogen synthase kinase-3 β and retinoblastoma protein, ... CERK was later confirmed to bind calmodulin in the presence of calcium, indicating the calmodulin first binds calcium and then ...
... encoding protein Calcium/calmodulin dependent protein kinase II inhibitor 1 CAMTA1 (1p36) CASP9 (1p36) CASZ1 (1p36): Castor ... encoding protein Zfp69 zinc finger protein ZMYM1 encoding protein Zinc finger MYM-type containing 1 ZNF436: Zinc finger protein ... encoding protein Mitogen-activated protein kinase kinase kinase 6 MEAF6: MYST/ESA1 associated factor 6 MECR: Trans-2-enoyl-CoA ... BED-type containing 6 ZC3H11A: Zinc finger CCCH domain-containing protein 11A ZNF648 encoding protein Zinc finger protein 648 ...
ITP3K activity is indirectly stimulated by phosphorylation by calcium/calmodulin-dependent kinase II (CaMKII). In addition, ... and these studies revealed various feedback mechanisms by which the enzyme is regulated by calcium and protein kinases. In 1999 ... the gene becomes expressed in a number of cancer cell types. In most cases, ITP3K expression causes the cancer to be more ... ITP3Ks are stimulated directly by calcium/calmodulin (Ca2+/CaM) binding. Generally, mammalian ITP3Ks are activated by calcium ...
Barry FA, Gibbins JM (Apr 2002). "Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI". The ... Andrews RK, Suzuki-Inoue K, Shen Y, Tulasne D, Watson SP, Berndt MC (Jun 2002). "Interaction of calmodulin with the cytoplasmic ... Collagen fibers are the most thrombogenic macromolecular components of the extracellular matrix, with collagen types I, III, ... "Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the ...
"Structure and expression of a calcium-binding protein gene contained within a calmodulin-regulated protein kinase gene". ... encodes myosin light chain kinase which is a calcium/calmodulin dependent enzyme. Four transcript variants that produce four ... Reaction type: phospho group transfer) It requires Ca2+ and calmodulin for activity. The 20-kDa light chain from smooth muscle ... "Kinase-related protein (telokin) is phosphorylated by smooth-muscle myosin light-chain kinase and modulates the kinase activity ...
2005). "Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B ... 2007). "Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes ... 2001). "Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)- ... portray Densin-180 as a key interactor in the midst of receptor proteins, scaffolding proteins and structural proteins. [number ...
... independent pathway involving calcium-binding protein 39 (Cab39) and serine threonine kinase with no lysine member 4 (WNK4) in ... WNK4 enhances TRPV5 by increasing its forward trafficking to the plasma membrane in a kinase-dependent manner. The inhibitory ... However, when Ca2+ levels are elevated, Ca2+/calmodulin complex binds to the C-terminal region, derepressing WNK4 kinase ... August 2005). "A new kindred with pseudohypoaldosteronism type II and a novel mutation (564D>H) in the acidic motif of the WNK4 ...
"CAMK2A calcium/calmodulin dependent protein kinase II alpha [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. ... β CAMKIIδ CAMKIIγ CAMKIII CAMKIV CAMKV CaM kinase like vesicle associated SCAMK Ca2+/calmodulin-dependent protein kinase kinase ... CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. ... Hudmon A, Schulman H (2002-06-01). "Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and ...
Voltage-gated calcium channels (VGCCs) are important mediators of pain hypersensitivity during inflammatory states, but their ... Voltage-gated calcium channels (VGCCs) are important mediators of pain hypersensitivity during inflammatory states, but their ... Elevated intracellular Ca2+ triggers various signaling pathways including protein kinases such as Calmodulin-dependent kinases ... low level NGF receptor stimulation and activation of calcium/calmodulin-dependent protein kinase. J. Neurosci. 15, 5966-5975. ...
Type 2 diabetes mellitus is associated with increased body weight, sleep problems and increased long-term mortality. Here, we ... Mammalian tribbles pseudokinase (TRIB) genes have also been linked to insulin resistance and type 2 diabetes mellitus. ... Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. Both Drosophila ... Furthermore, it decreases the levels of Drosophila insulin-like peptide 2 (DILP2; ILP2) and increases night-time sleep. The ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 100% * Ion Channels 99% * Hyperglycemia 92% ... Early Recognition of Type 2 Diabetes Complications and Use of SGLT2i in Multidisciplinary Approach: Indonesian Perspective - An ... The correlation between high sensitivity C-reactive protein level and the extent of coronary lesion and cardiac systolic ... Correlation of Serum Ferritin and Cardiac Iron Toxicity with Cardiac Function in Transfusion Dependent Beta-Thalassemia Major ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 14% * Excitatory Amino Acids 13% ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 Medicine & Life Sciences 98% * Acute Lung Injury Medicine & Life Sciences 88 ... Cecal Ligation Puncture (CLP) was used to induce preclinical septic ALI in wild-type mice and mice deficient in NOX2 or p47phox ... Cecal Ligation Puncture (CLP) was used to induce preclinical septic ALI in wild-type mice and mice deficient in NOX2 or p47phox ... Cecal Ligation Puncture (CLP) was used to induce preclinical septic ALI in wild-type mice and mice deficient in NOX2 or p47phox ...
... in calcium promotes the formation of calcium-calmodulin complexes that activate a number of kinases as well as protein ... Alternatively, CD8-positive CTLs can also use the Fas-dependent pathway to induce cytolysis and apoptosis. The Fas pathway is ... The degree and type of response also vary with the type of the transplant. Some sites, such as the eye and the brain, are ... It binds to a different intracellular protein (FK Binding Protein-12 [FKBP-12]) than cyclosporine but has the same mechanism of ...
Protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) have been identified as potential mediators of ... All of eDissFaculties & ProgramsIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesTypeThis FacultyIssue DateAuthorAdvisor & ... The resulting increased spontaneous diastolic calcium release promotes arrhythmic events and compromises cardiac contractility ... Die Bedeutung der Proteinkinase A und der Ca2+/Calmodulin abhängigen Proteinkinase II für das Sarkoplasmatische Retikulum ...
Here we show that calcium/calmodulin-dependent protein kinase ID (CaMK1D), a genetic hot spot in type 2 diabetes, is activated ... mRNA and protein content of NPY and its receptors were assessed in GCs from DHT treated rats using RT-qPCR and Western blot, ... RESULTS: A dose-dependent increase in appetite was observed after the injection of adiponectin (20.73, 41.45, and 62.18 nmol) ( ... The G-protein-coupled Y4-receptor (Y4R) and its endogenous ligand, pancreatic polypeptide (PP), suppress appetite in response ...
Calcium/calmodulin-Dependent Protein Kinase II Inhibitor 1 (aa 1-78) Protein, tagged with His tag. ... Calcium/calmodulin-Dependent Protein Kinase II Inhibitor 1 (aa 1-78) Protein, tagged with His tag. ... The coronavirus genome encodes a spike protein, an envelope protein, a membrane protein, and a nucleoprotein. Among them, spike ... Type. *Inhibitor. *Applications. *Crystallization (Crys), ELISA, SDS-PAGE (SDS), Western Blotting (WB) ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2. _. Top Journals Top journals in which articles about this concept have been ... Probing human heart TCA cycle metabolism and response to glucose load using hyperpolarized [2-13 C]pyruvate MRS. NMR Biomed. ...
calcium/calmodulin-dependent protein kinase II inhibitor 1; ZFN induced mutant 1, Tja. IMP. RGD. PMID:31327268. RGD:18899561. ... compared to wild type. RGD. PMID:26077568. RGD:13800514. G. Lamp2. lysosomal-associated membrane protein 2. IMP. in hemizygote ... calcium/calmodulin-dependent protein kinase II inhibitor 1. IMP. RGD. PMID:31327268. RGD:18899561. NCBI chr 5:150,674,819... ... bone morphogenetic protein receptor type 2; ZFN induced mutant 1, Ang. IMP. RGD. PMID:25593290. RGD:38500244. ...
... calmodulin (CaM) signaling is important for a wide range of cellular functions. It is not surprised the role of this signaling ... Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a ... Calcium/calmodulin-dependent protein kinase II. Biochem J. 1989;258(2):313-25.. 7. Sun P, Enslen H, Myung PS, Maurer RA. ... calmodulin-dependent protein kinase IV. Endocrinology. 2000;141(12):4777-83.. 52. Wu JY, Means AR. Ca(2+)/calmodulin-dependent ...
Full Name: Calcium/calmodulin-dependent protein kinase type II subunit alpha O-GlcNAc Score: ...
c-Abl Protein Kinase and Imatinib Calcium Pump. Calmodulin. cAMP-dependent Protein Kinase (PKA) ... Inhibitors of dipeptidyl peptidase 4 are used to treat type-2 diabetes ... cAMP-dependent Protein Kinase (PKA) PKA delivers cellular signals by adding phosphates to proteins ... RAF Protein Kinases A single mutation in a RAF protein kinase can help transform a normal cell into a cancer cell. ...
... mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no ... Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that ... mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no ... Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that ...
Protein Ontology. PR:000003200 calcium/calmodulin-dependent protein kinase type II subunit beta ... and chromosome location of the gene for the beta subunit of brain-specific Ca2+/calmodulin-dependent protein kinase II ... protein coding gene. Chr11:5919642-6016401 (-). 129S1/SvImJ MGP_129S1SvImJ_G0018014. protein coding gene. Chr11:3064160-3157810 ... protein coding gene. Chr11:2965892-3058931 (-). C57BL/6NJ MGP_C57BL6NJ_G0018407. protein coding gene. Chr11:3142571-3242742 (-) ...
Calcium/calmodulin-dependent protein kinase II alpha. CSF-1:. Colony stimulating factor-1 ... Studies have shown that DNMT1 is abnormally expressed in many tumor types [64, 65], and their regulation by miR-148/152 family ... Xie B, He SW, Wang XD: Effect of gastrin on protein kinase C and its subtype in human colon cancer cell line SW480. World J ... coiled-coil containing protein kinase 1(ROCK1), which might be a target of miR-148a, was involved in miR-148a-induced ...
... and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, ... type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent ... GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. ... A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of ...
... reversible inhibition of L-type calcium channels. Biochem. Biophys. Res. Commun.345, 1606-1610. ... Regulation of multifunctional Ca2+/calmodulin-dependent protein kinases by Ca2+/calmodulin-dependent protein kinase phosphatase ... Phosphorylation and activation of Ca2+/calmodulin-dependent protein kinase phosphatase by Ca2+/calmodulin-dependent protein ... Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes ...
... and G-proteins in pear) and interconnected hormonal signaling (jasmonic acid in pear, auxins in apple and brassinosteroids in ... Signal transduction was triggered in both species with calcium ( ... calmodulin dependent protein kinase (CPK) (CPK8 and CPK28 in ... calcium-dependent protein kinase; DFR, dihydroflavonol reductase; F3H, flavanone 3-hydroxylase; FLS, flavonol synthase; HCT, ... Some G-proteins are known to interact with Plant U-box type E3 ubiquitin ligases (PUBs), implicated in the regulation of the ...
Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular ... In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel ... Functional consequence of protein kinase A-dependent phosphorylation of the cardiac ryanodine receptor: sensitization of store ... Protein Function Uniprot: Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the ...
Animals, Base Sequence, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein ... Rapid superfusion of immobilized Ca2+- and calmodulin-dependent protein kinase II (CaM kinase II) in vitro showed that the ... Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations.. Publication Type:. Journal Article ... Kinases, Calmodulin, Cercopithecus aethiops, COS Cells, Enzyme Activation, Enzymes, Immobilized, Molecular Sequence Data, ...
We also found that G1 expression induces AMPK phosphorylation via Ca2+/calmodulin-dependent protein kinase II (CaMKII) and that ... Second, while we (21) and others (22, 23, 26, 27) have previously reported that expression of APOL1 RRV in various cell types ... APOL1 G1 activates Gαq-PLC-IP3R/RYR signaling to liberate calcium from the ER into the cytosol of T-REx-293 cells. (A) Fura-2 ... APOL1 risk allele RNA contributes to renal toxicity by activating protein kinase R. Commun Biol. 2018;1:188. View this article ...
Ca2+/CaM kinase II. Ca2+/calmodulin-dependent protein kinase II. DA. dopamine. DAT. dopamine transporter. DTG. 1,3-di(2-tolyl) ... voltage-dependent calcium channel. ω-CgTX. ω-conotoxin from Conus geographus(GVIA). DMEM. Dulbeccos Modified Eagle Medium. ... However, two inhibitors of Ca2+/calmodulin-dependent protein kinase II blocked enhancement in AMPH-stimulated release by (+)- ... The source of Ca2+ required for the enhancement of reverse transport did not appear to be via N- or L-type voltage-dependent Ca ...
... calmodulin-dependent protein kinase II. // J. Biol. Chem. 1993,268:7863-7867. ... mGluRl-mediated potentiation of NMDA receptors involves a rise in intracellular calcium and activation of protein kinase C. // ... The NMDA type glutamate receptors expressed by primary rat osteoblasts have the same electrophysiological characteristics as ... Leonard A.S., Hell J.W. Cyclic AMP-dependent protein kinase and protein kinase С phosphorylate N-methyl-D-aspartate receptors ...
Calcium-dependent signaling pathways and heat shock protein expression regulate dimorphism in Paracoccidioides brasiliensis and ... with a heat shock protein 70-type profile, initiates the assembly of proteins necessary for mycelial growth. ... Yeast-form-specific genes identified in Histoplasma capsulatum function in calcium/calmodulin signaling pathways and sulphur ... Heat shock proteins are emphasized because of the temperature-sensitive morphogenesis to the tissue form. ...
Calcium-dependent signaling pathways and heat shock protein expression regulate dimorphism in Paracoccidioides brasiliensis and ... with a heat shock protein 70-type profile, initiates the assembly of proteins necessary for mycelial growth. ... Yeast-form-specific genes identified in Histoplasma capsulatum function in calcium/calmodulin signaling pathways and sulphur ... Heat shock proteins are emphasized because of the temperature-sensitive morphogenesis to the tissue form. ...
... or cGMP-dependent protein kinase; and threonine 17 (Thr17), by Ca2+-calmodulin-dependent protein kinase. Phosphorylation of PLN ... Histidine-Rich Calcium Binding Protein and the S96A Human Variant. The histidine-rich Ca binding protein (HRC), a 165 kD SR ... hypertrophy is attenuated and there is no decompensation in the transgenics compared with wild-type controls. These studies in ... SR Calcium Cycling Protein Genetic Variants in Human Heart Failure. Our basic studies have recently been extended to the ...
Promotion of Calcium/calmodulin-dependent protein kinase 4 promotes GLUT1-dependent glycolysis in systemic lupus erythematosus ... Nakamura H, Shimizu T, Takatani A, Suematsu T, Nakamura T, Kawakami A. Initial human T-cell leukemia virus type 1 infection of ... Lupus Nephritis IgG Induction of Calcium/Calmodulin-Dependent Protein Kinase IV Expression in Podocytes and Alteration of Their ... Anti-citrullinated protein antibody titre as a predictor of abatacept treatment persistence in patients with rheumatoid ...
  • When activated, the enzymes transfer phosphates from ATP to defined serine or threonine residues in other proteins, so they are serine/threonine-specific protein kinases. (wikipedia.org)
  • They are multifunctional serine/threonine protein kinases that regulate the development and activity of different kinds of cell types through a variety of substrates [ 6 - 8 ]. (scientificarchives.com)
  • 114180)-dependent protein kinases (CAMKs) are a subfamily of the serine/threonine protein kinase household. (ergudenltd.com)
  • Eukaryotes have developed a highly adaptive complex, the serine/threonine kinase adenosine monophosphate (AMP)-activated protein kinase (AMPK), to sense low cellular adenosine triphosphate (ATP) levels [ 1 ] . (encyclopedia.pub)
  • The elevation in [Ca2+]i activates the calcium/calmodulin-sensitive myosin light chain kinase (MLCK), leading to phosphorylation of the regulatory myosin light chain (MLC20) at Serine 19. (asknevillesouthall.com)
  • This calcium saturation activates the kinase and allows it to undergo a conformational change which permits the kinase to bind to its phosphorylation target sites. (wikipedia.org)
  • These groups allow for the CaM-dependent phosphorylation of targets, but also allows the structure to autophosphorylate itself and become CaM-independent, as seen in Figure 1. (wikipedia.org)
  • CaMKs have a special phosphorylation-dependent mechanism for the regulation of kinase activity. (scientificarchives.com)
  • Functional consequence of protein kinase A-dependent phosphorylation of the cardiac ryanodine receptor: sensitization of store overload-induced Ca2+ release. (univ-amu.fr)
  • PKC phosphorylation of these proteins also inhibits their binding to RNA in vitro. (embl.de)
  • Analyses of changes in transcription and protein phosphorylation suggest that hypothyroidism prolonged expression of fibroblast growth factor receptors, and decreased phosphorylated Cofilin. (springer.com)
  • Nikolaienko O, Eriksen MS, Patil S, Bito H, and Bramham CR (2017) Stimulus-evoked ERK-dependent phosphorylation of activity-regulated cytoskeleton-associated protein (Arc) regulates its neuronal subcellular localization. (uib.no)
  • A possible mechanism involves the small monomeric G protein Rho that can augment ASM contractility by increasing levels of MLC phosphorylation via the Rho-activated kinase (ROCK) dependent suppression of MLC phosphatase (26, 27). (asknevillesouthall.com)
  • Calcium-saturated calmodulin (CaM) directly activates CaM-dependent protein kinase I (CaMKI) by binding to a region in the C-terminal regulatory sequence of the enzyme to relieve autoinhibition. (rcsb.org)
  • Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor. (univ-amu.fr)
  • The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. (univ-amu.fr)
  • Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2. (univ-amu.fr)
  • Open in a separate window Physique 1 Excitation-contraction coupling in airway easy muscleEffects of pro-inflammatory cytokines and 2-adrenergic receptor agonists on excitation-contraction coupling in ASM cells. (asknevillesouthall.com)
  • 2-adrenergic receptor agonists regulate calcium homeostasis and calcium sensitization by inhibiting RhoA activation, Ca2+ release from the sarcoplasmic reticulum, and actin-myosin crossbridging. (asknevillesouthall.com)
  • 2AR, 2-adrenergic receptor. (asknevillesouthall.com)
  • Roles of the G protein-coupled receptor kinase 2 and Rab5 in α1B-adrenergic receptor function and internalization. (mutagenex.com)
  • Glycogen Synthase Kinase-3 modulates α1A-adrenergic receptor action and regulation. (mutagenex.com)
  • Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. (lookformedical.com)
  • By contrast, the other cannabinoid receptor subtype, the CB(2) receptor, shows a much more restricted distribution and is absent from normal brain. (lookformedical.com)
  • Of interest, the extent of CB(2) receptor expression was directly related with tumor malignancy. (lookformedical.com)
  • Experiments carried out with C6 glioma cells in culture evidenced the internalization of the CB(2) but not the CB(1) receptor upon JWH-133 challenge and showed that selective activation of the CB(2) receptor signaled apoptosis via enhanced ceramide synthesis de novo. (lookformedical.com)
  • This synergistic effect was reduced by the CB(2) cannabinoid receptor antagonist SR144528, although PEA does not activate either CB(1) or CB(2) receptors. (lookformedical.com)
  • This effect was not blocked by the CB(2) receptor antagonist SR144528, and was not mimicked by a selective agonist of CB(2) receptors. (lookformedical.com)
  • Members of the CAMK enzyme class include, but are not limited to: CAMKI CAMKIα (CAMK1) CAMKIβ (PNCK) CAMKIδ CAMKIγ (CAMK1G) CAMKII CAMKIIα CAMKIIβ CAMKIIδ CAMKIIγ CAMKIII CAMKIV CAMKV CaM kinase like vesicle associated SCAMK Ca2+/calmodulin-dependent protein kinase kinase CAMKK1 CAMKK2 Pseudokinases are pseudoenzymes, proteins that resemble enzymes structurally, but lack catalytic activity. (wikipedia.org)
  • The difference is, for CaMKII, the Thr-286 residue in the regulatory domain is auto- phosphorylated before kinase activation. (scientificarchives.com)
  • These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. (lvhn.org)
  • CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. (wikipedia.org)
  • The multifunctional Ca 2+ /CaM-dependent protein kinases (CaMKs) are critical intermediates of this signaling and play key roles in cancer development. (scientificarchives.com)
  • However, based on their substrate specificity, not all CaM-regulated kinases are Ca 2+ /CaMdependent protein kinases (CaMKs). (scientificarchives.com)
  • The ADP/ATP binding site locates between the small and large lobes of CaMKs' kinase domains. (scientificarchives.com)
  • The level of intracellular calcium regulates, in part, ASM shortening. (asknevillesouthall.com)
  • Activation of an ASM cell by an agonist induces a rapid rise in [Ca2+]i, associated with the release of intracellular calcium stores, to a peak level roughly tenfold higher than the resting level (100 nM to greater than 1 M with maximum agonist stimulation). (asknevillesouthall.com)
  • Substrate-specific CAM Kinases only have one target that they can phosphorylate, such as myosin light chain kinases. (wikipedia.org)
  • CAMK II is the main protein in this subset. (wikipedia.org)
  • Figure 1 shows how the presence of calcium or calmodulin allows for the activation of CAM kinases (CAMK II). (wikipedia.org)
  • Figure 2 goes into detail showing the structure and domains of CAMK I. CAMK II has a variety of different forms, with CAMK 2A being the most common, as shown in Figure 3. (wikipedia.org)
  • A further chapter discusses how surface membrane G-protein receptors in C. albicans and other fungi transmit external stimuli through 2 major protein kinase cascades. (cdc.gov)
  • Contractile agonists activate receptors that influence intracellular signaling, affecting calcium homeostasis and sensitization as well as the function and expression of GPCRs and CD38. (asknevillesouthall.com)
  • Inflammatory cytokines bind to receptors and modulate calcium homeostasis by increasing expression of CD38 and increasing Ca2+ release from the sarcoplasmic reticulum. (asknevillesouthall.com)
  • Studies using cultured human tracheal or bronchial easy muscle cells, as models of ASM responsiveness, convincingly exhibited that Gq-protein coupled receptors (GPCR)-associated signaling in ASM can be modulated by a variety of inflammatory stimuli. (asknevillesouthall.com)
  • Microarray technology used to study the modulation of gene expression of ASM by IL-13 revealed a diversity of potential molecular mechanisms influencing ASM responsiveness, including changes in cytoskeletal proteins, receptors or calcium regulators (24). (asknevillesouthall.com)
  • PEA did not modify the affinity of ligands for CB(1) or CB(2) receptors, and neither did it alter the CB(1)/CB(2)-mediated inhibitory effect of AEA on adenylate cyclase type V, nor the expression of CB(1) and CB(2) receptors in MCF-7 cells. (lookformedical.com)
  • It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 in yeast, and SnRK1 in plants. (encyclopedia.pub)
  • Eukaryotic Tribbles proteins are pseudoenzymes that regulate multiple aspects of intracellular signalling. (cam.ac.uk)
  • Calcium-dependent signaling pathways and heat shock protein expression regulate dimorphism in Paracoccidioides brasiliensis and have broad implications for other pathogens. (cdc.gov)
  • These data suggest that PKC may regulate interactions of EWS and other RNA-binding proteins with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing. (embl.de)
  • Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. (bvsalud.org)
  • We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. (bvsalud.org)
  • Ca 2+ / calmodulin (CaM) signaling is important for a wide range of cellular functions. (scientificarchives.com)
  • Calcium (Ca 2+ ) is an intracellular universal second messenger that regulates a variety of cellular processes. (scientificarchives.com)
  • Required for cellular calcium ion homeostasis. (univ-amu.fr)
  • Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. (embl.de)
  • Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. (embl.de)
  • Adenosine monophosphate-activated protein kinase (AMPK) is in charge of numerous catabolic and anabolic signaling pathways to sustain appropriate intracellular adenosine triphosphate levels in response to energetic and/or cellular stress. (encyclopedia.pub)
  • 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. (encyclopedia.pub)
  • Early steps in this transition are complex, with at least 2 signaling pathways identified: 1 stops yeast growth and another, with a heat shock protein 70-type profile, initiates the assembly of proteins necessary for mycelial growth. (cdc.gov)
  • Yeast-form-specific genes identified in Histoplasma capsulatum function in calcium/calmodulin signaling pathways and sulphur metabolism. (cdc.gov)
  • In a current acquisition damage, only 500 Defects of complex is required to bind pathways chloride-dependent. (erik-mill.de)
  • Inflammatory cytokines such as IL-13, IL-1 and TNF- also increase Rho kinase activity to modulate the calcium sensitization pathways. (asknevillesouthall.com)
  • All kinases have a common structure of a catalytic core including an ATP binding site along with a larger substrate binding site. (wikipedia.org)
  • CAMK I as shown in Figure 2, has a double-lobed structure, consisting of a catalytic, substrate-binding domain and an autoinhibitory domain. (wikipedia.org)
  • For the autoinhibitory domain to become functional, it must cause the protein to conform in such a way that this domain completely blocks the substrate domain from taking in new targets. (wikipedia.org)
  • Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. (embl.de)
  • Short calmodulin-binding motif containing conserved Ile and Gln residues. (embl.de)
  • A modified version of the IQ motif as a consensus for Ca2+-independent binding and two related motifs for Ca2+-dependent binding, termed 18-14 and 1-5-10 based on the position of conserved hydrophobic residues, are proposed. (embl.de)
  • Thus, the kinase activation mechanism involves the binding of CaM to residues associated with the inhibitory pseudosubstrate sequence. (rcsb.org)
  • Following this peak, calcium levels fall but remain elevated provided that the excitatory stimulus remains present. (asknevillesouthall.com)
  • The heart is constituted by three types of muscle: atrial, ventricular, and specialized excitatory and conducting fibers. (bvsalud.org)
  • protein_coding" "Cz05g36130.t1","No alias","Chromochloris zofingiensis","Membrane insertase YidC/ALB3/OXA1/COX18 [Interproscan]. (ntu.edu.sg)
  • At this Overexpression the wide membrane meets signaling FGFR1 3' kinases of 2-3 topics. (erik-mill.de)
  • Sequence motifs for calmodulin recognition. (embl.de)
  • Although considerable sequence diversity is observed among the different binding regions, these three classes of recognition motifs exist for many of the known CaM binding proteins. (embl.de)
  • The CaM-peptide affinity is approximately 1 pM, compared with 30 nM for the CaM-kinase complex, indicating that activation of autoinhibited CaMKI by CaM requires a costly energetic disruption of the interactions between the CaM-binding sequence and the rest of the enzyme. (rcsb.org)
  • For example, the once called CaMKIII is now termed eukaryotic elongation factor 2 (eEF2) kinase, due to containing a small number of substrates [ 5 ]. (scientificarchives.com)
  • Multi-functional CAM Kinases have multiple targets they can phosphorylate and are found in processes including the secretion of neurotransmitters, metabolism of glycogen, and the regulation of various transcription factors. (wikipedia.org)
  • We aim to uncover the logic of synaptic plasticity at the level of protein synthesis, protein functional properties, and the dynamics of protein interaction networks. (uib.no)
  • Here we report that EWS, a nuclear RNA-binding prooncoprotein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin. (embl.de)
  • Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. (univ-amu.fr)
  • Once calcium concentrations in the cell rise, CAM kinases become saturated and bind the maximum of four calcium molecules. (wikipedia.org)
  • The CAM Kinase contains a highly concentrated glycine loop where the gamma phosphate from the donor ATP molecule is easily able to bind to the enzyme which then utilizes the metal ion to facilitate a smooth phosphate transfer to the target protein. (wikipedia.org)
  • Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. (embl.de)
  • Mammalian tribbles pseudokinase (TRIB) genes have also been linked to insulin resistance and type 2 diabetes mellitus. (cam.ac.uk)
  • Next we compared gene expression profiles of Foxp3+ Treg subsets (+) of different maturity (24lo, 24int, 24hi) and could identify a set of genes that were specifically up or downregulated in Foxp3+ Tregs, but not in Foxp3- conventional T cells, in a maturation-dependent manner. (gsea-msigdb.org)
  • It consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans. (encyclopedia.pub)
  • Pilliod J, Desjardins A, Pernègre C, Jamann H, Larochelle C, Fon EA, Leclerc N. Clearance of intracellular tau protein from neuronal cells via VAMP8-induced secretion. (mutagenex.com)
  • There are 2 common types of CAM Kinase proteins: specialized and multi-functional CAM kinases. (wikipedia.org)
  • Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)
  • In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. (univ-amu.fr)
  • Ca 2+ signaling works by forming a complex with calmodulin (CaM), a 148-amino-acid protein that transduces signals in response to intracellular Ca 2+ elevation. (scientificarchives.com)
  • FA core complex associated protein. (gsea-msigdb.org)
  • In the download جبر, the possible proteins of these two proteinases are in permeable regulators, flooding nucleotides that attract packaged to the protein and secreted to complex credits via the cytosolic death. (erik-mill.de)
  • The function and mechanism of these kinases in leukemia development are summarized in this study. (scientificarchives.com)
  • protein_coding" "Cz04g07200.t1","No alias","Chromochloris zofingiensis","Domain of unknown function DUF4201 [Interproscan]. (ntu.edu.sg)
  • Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. (lvhn.org)
  • Lead absorption is augmented in the presence of iron, zinc, and calcium deficiency. (medscape.com)
  • Most all CAM kinases includes a variety of domains, including: a catalytic domain, a regulatory domain, an association domain, and a calcium/calmodulin binding domain. (wikipedia.org)
  • CAMK removes a phosphate group from ATP, most typically using a Mg2+ ion, and adds it to the CAM protein, rendering it active. (wikipedia.org)
  • Signal transduction was triggered in both species with calcium (and G-proteins in pear) and interconnected hormonal signaling (jasmonic acid in pear, auxins in apple and brassinosteroids in both species), without involvement of salicylic acid. (biomedcentral.com)
  • Objective -To determine whether expression of G proteins (G i and G s ) is altered in thyroid gland adenomas obtained from hyperthyroid cats. (avma.org)