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.

Inhibition of the Ca2+/calmodulin-dependent protein kinase I cascade by cAMP-dependent protein kinase. (1/105)

Several recent studies have shown that Ca2+/calmodulin-dependent protein kinase I (CaMKI) is phosphorylated and activated by a protein kinase (CaMKK) that is itself subject to regulation by Ca2+/calmodulin. In the present study, we demonstrate that this enzyme cascade is regulated by cAMP-mediated activation of cAMP-dependent protein kinase (PKA). In vitro, CaMKK is phosphorylated by PKA and this is associated with inhibition of enzyme activity. The major site of phosphorylation is threonine 108, although additional sites are phosphorylated with lower efficiency. In vitro, CaMKK is also phosphorylated by CaMKI at the same sites as PKA, suggesting that this regulatory phosphorylation might play a role as a negative-feedback mechanism. In intact PC12 cells, activation of PKA with forskolin resulted in a rapid inhibition of both CaMKK and CaMKI activity. In hippocampal slices CaMKK was phosphorylated under basal conditions, and activation of PKA led to an increase in phosphorylation. Two-dimensional phosphopeptide mapping indicated that activation of PKA led to increased phosphorylation of multiple sites including threonine 108. These results indicate that in vitro and in intact cells the CaMKK/CaMKI cascade is subject to inhibition by PKA-mediated phosphorylation of CaMKK. The phosphorylation and inhibition of CaMKK by PKA is likely to be involved in modulating the balance between cAMP- and Ca2+-dependent signal transduction pathways.  (+info)

Ca(2+)/Calmodulin-dependent protein kinase cascade in Caenorhabditis elegans. Implication in transcriptional activation. (2/105)

We have recently demonstrated that Caenorhabditis elegans Ca(2+)/calmodulin-dependent protein kinase kinase (CeCaM-KK) can activate mammalian CaM-kinase IV in vitro (Tokumitsu, H., Takahashi, N., Eto, K., Yano, S., Soderling, T.R., and Muramatsu, M. (1999) J. Biol. Chem. 274, 15803-15810). In the present study, we have identified and cloned a target CaM-kinase for CaM-KK in C. elegans, CeCaM-kinase I (CeCaM-KI), which has approximately 60% identity to mammalian CaM-KI. CeCaM-KI has 348 amino acid residues with an apparent molecular mass of 40 kDa, which is activated by CeCaM-KK through phosphorylation of Thr(179) in a Ca(2+)/CaM-dependent manner, resulting in a 30-fold decrease in the K(m) of CeCaM-KI for its peptide substrate. Unlike mammalian CaM-KI, CeCaM-KI is mainly localized in the nucleus of transfected cells because the NH(2)-terminal six residues ((2)PLFKRR(7)) contain a functional nuclear localization signal. We have also demonstrated that CeCaM-KK and CeCaM-KI reconstituted a signaling pathway that mediates Ca(2+)-dependent phosphorylation of cAMP response element-binding protein (CREB) and CRE-dependent transcriptional activation in transfected cells, consistent with nuclear localization of CeCaM-KI. These results suggest that the CaM-KK/CaM-KI cascade is conserved in C. elegans and is functionally operated both in vitro and in intact cells, and it may be involved in Ca(2+)-dependent nuclear events such as transcriptional activation through phosphorylation of CREB.  (+info)

The expression of Ca2+/calmodulin-dependent protein kinase I in rat retina is regulated by light stimulation. (3/105)

Ca2+/calmodulin-dependent protein kinase I (CaM-kinase I) in rat retina was analyzed by immunohistochemical analysis, Western blot analysis and kinase activity assay. Western blot analysis revealed two immunoreactive bands similar to those detected in the brain. Developmental studies revealed that CaM-kinase I expression increased in accordance with postnatal development. Expression of CaM-kinase I in the retinas of rats raised in the complete darkness markedly decreased. CaM-kinase I activity assay supported these findings. Synapsin I was shown to be a possible intrinsic substrate of CaM-kinase I in rat retina. These results elucidated that CaM-kinase I is expressed in the retina and may play an important role in the retinal functions and that the expression of CaM-kinase I is regulated by light stimulation.  (+info)

Increased expression of Galphaq protein in the heart of streptozotocin-induced diabetic rats. (4/105)

Heart disease is one of the major cause of death in diabetic patients, but the pathogenesis of diabetic cardio-myopathy remains unclear. In this experiment, to assess the significance of G protein signaling pathways in the pathogenesis of diabetic cardiomyopathy, we analyzed the expression of G proteins and the activities of second messenger dependent protein kinases: cAMP-dependent protein kinase (PKA), DAG-mediated protein kinase C (PKC), and calmodulin dependent protein kinase II (CaM kinase II) in the streptozotocin induced diabetic rat heart. The expression of Galphaq was increased by slightly over 10% (P<0.05) in diabetic rat heart, while Galphas, Galphai, and Gbeta remained unchanged. The PKA activity in the heart did not change significantly but increased by 27% (P<0.01) in the liver. Insulin treatment did not restore the increased activity in the liver. Total PKC activity in the heart was increased by 56% (P<0.01), and insulin treatment did not restore such increase. The CaM kinase II activity in the heart remained at the same level but was slightly increased in the liver (14% increase, P<0.05). These findings of increased expression of Galphaq in the streptozotocin-diabetic rat heart that are reflected by the increased level of PKC activity and insensitivity to insulin demonstrate that alteration of Galphaq may underlie, at least partly, the cardiac dysfunction that is associated with diabetes.  (+info)

Regulation of phenobarbital induction of the cytochrome P450 2b9/10 genes in primary mouse hepatocyte culture. Involvement of calcium- and cAMP-dependent pathways. (5/105)

Phenobarbital (PB) has long been known as an inducer of drug-metabolizing enzymes in liver, but the molecular mechanism underlying this induction is still poorly understood. Using primary mouse hepatocyte culture, we have investigated the possible involvement of different regulatory pathways in PB action, by exposing PB-treated cells to various protein kinase/phosphatase modulators. Our results showed a negative role of the cAMP-dependent pathway, as treatment with cAMP-dependent protein kinase (PKA) activators (10 microM dibutyryl-cAMP and 50 microM forskolin) dramatically inhibited PB-induced Cyp2b9/10 mRNA accumulation, whereas PKA inhibitor potentiated the PB responsiveness of this gene. The cGMP-dependent protein kinase (PKG) seems to play a positive role as PKG inhibitor reduced the PB-induced level of Cyp2b9/10 mRNA. We also obtained two lines of evidence for the involvement of Ca2+ in modulating PB action. Firstly, measurements of intracellular Fura-2 fluorescence ratio in murine hepatocytes showed that long-term PB incubation (24 and 48 h) led to a significant increase of [Ca2+]i. Secondly, treatment with an intracellular Ca2+ chelator (BAPTA-AM) nearly completely abolished PB-induced Cyp2b9/10 expression. Ca2+ thus appeared to mediate PB action likely via Ca2+/calmodulin-dependent protein kinase II, as KN62, a specific inhibitor of this enzyme, also dramatically inhibited PB induction of the Cyp2b9/10 genes.  (+info)

Activation of orphan receptor-mediated transcription by Ca(2+)/calmodulin-dependent protein kinase IV. (6/105)

Retinoid-related receptor alpha (RORalpha) is an orphan nuclear receptor that constitutively activates transcription from its cognate response element. We show that RORalpha is Ca(2+ )responsive, and a Ca(2+)/calmodulin-independent form of Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) potentiates RORalpha-dependent transcription 20- to 30-fold. Other orphan receptors including RORalpha2, RORgamma and COUP-TFI are also potentiated by CaMKIV. Transcriptional activation by CaMKIV is orphan receptor selective and does not occur with either the thyroid hormone or estrogen receptor. CaMKIV does not phosphorylate RORalpha or its ligand-binding domain (LBD) in vitro, although the LBD is essential for transactivation. Therefore, the RORalpha LBD was used in the mammalian two-hybrid assay to identify a single class of small peptide molecules containing LXXLL motifs that interacted with greater affinity in the presence of CaMKIV. This class of peptides antagonized activation of orphan receptor-mediated transcription by CaMKIV. These studies demonstrate a pivotal role for CaMKIV in the regulation of orphan receptor-mediated transcription.  (+info)

Variation of phospholamban in slow-twitch muscle sarcoplasmic reticulum between mammalian species and a link to the substrate specificity of endogenous Ca(2+)-calmodulin-dependent protein kinase. (7/105)

Systematic immunological and biochemical studies indicate that the level of expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase regulatory protein phospholamban (PLB) in mammalian slow-twitch fibers varies from zero, in the rat, to significant levels in the rabbit, and even higher in humans. The lack of PLB expression in the rat, at the mRNA level, is shown to be exclusive to slow-twitch skeletal muscle, and not to be shared by the heart, thus suggesting a tissue-specific, in addition to a species-specific regulation of PLB. A comparison of sucrose density-purified SR of rat and rabbit slow-twitch muscle, with regard to protein compositional and phosphorylation properties, demonstrates that the biodiversity is two-fold, i.e. (a) in PLB membrane density; and (b) in the ability of membrane-bound Ca(2+)-calmodulin (CaM)-dependent protein kinase II to phosphorylate both PLB and SERCA2a (slow-twitch isoform of Ca(2+)-ATPase). The basal phosphorylation state of PLB at Thr-17 in isolated SR vesicles from rabbit slow-twitch muscle, colocalization of CaM K II with PLB and SERCA2a at the same membrane domain, and the divergent subcellular distribution of PKA, taken together, seem to argue for a differential heterogeneity in the regulation of Ca(2+) transport between such muscle and heart muscle.  (+info)

AMPA receptor-mediated, calcium-dependent CREB phosphorylation in a subpopulation of auditory neurons surviving activity deprivation. (8/105)

Although dependence on afferent synaptic activity has been shown for central neurons in every sensory system, the mechanisms of afferent maintenance of target sensory neurons are not understood. Neurons in the cochlear nucleus (CN) require afferent activity for maintenance and survival. One of the earliest changes seen after activity deprivation is an increase in intracellular calcium that leads to the death of 30% of the neuronal population. Sixty minutes after deafferentation, the surviving neurons show increased phosphorylation of the transcription factor calcium/cAMP response element-binding protein (CREB). CREB phosphorylation in activity-deprived CN neurons is dependent on increased intracellular calcium resulting from influx through AMPA receptors and is mediated by calcium/calmodulin-dependent kinases and protein kinase A. We conclude that in CN neurons, the deafferentation-induced increase in calcium activates at least two kinase pathways that phosphorylate CREB in surviving neurons. We hypothesize that this phosphorylation results in the transcription of genes containing the calcium/cAMP response element within their promoter regions, and these genes code for proteins that allow the neurons to compensate for their hypercalcemic, activity-deprived state.  (+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.

Calcium/calmodulin-dependent protein kinase type 1 is an enzyme that in humans is encoded by the CAMK1 gene. Calcium/calmodulin ... 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 ... Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly ...
Calcium/calmodulin-dependent protein kinase type 1... [more]. par-1. 4.800e-16. 29.93. Serine/threonine-protein kinase par-1 [ ... Calmodulin-dependent protein kinase; may play a ro... [more]. SNF1. 8.646e-12. 29.79. AMP-activated S/T protein kinase; forms a ... Calcium/calmodulin-dependent protein kinase type 1 [Source:UniProtKB/Swiss-Prot;Acc:Q9TXJ0]). HSP 1 Score: 73.9442 bits (180), ... Match: CMK1 (Calmodulin-dependent protein kinase; may play a role in stress response, many Ca++/calmodulin dependent ...
... phosphorylated-calcium/calmodulin-dependent protein kinase II (p-CaMKII), brain-derived neurotrophic factor (BDNF), ... type subunit 1 (GluA1), glutamate ionotropic receptor (AMPA) type subunit 2 (GluA2), phosphorylated voltage-gated potassium ... phosphorylated protein kinase B (p-AKT), phosphorylated extracellular signal-regulated kinase (p-ERK), CXC chemokine receptor 4 ... Protein analysis in the hippocampus suggests that AMPA-dependent alterations in BDNF-TrkB and Kv2.1 pathways may be involved in ...
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 kinase; PDK1, pyruvate dehydrogenase kinase 1; CRAC, calcium release-activated ... The type of reactive oxygen species (ROS) that activates adenosine monophosphate-activated protein kinase (AMPK). ATP, ... Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab ... Differential AMP-activated Protein Kinase (AMPK) Recognition mechanism of Ca2+/calmodulin-dependent protein kinase kinase ...
... 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 ...
... these proteins now comprise a family of at least 10. All of the membrane-bound enzymes are activated by the alpha subunit of G ... Calcium / metabolism * Cloning, Molecular * Cyclic AMP-Dependent Protein Kinases / genetics * Cyclic AMP-Dependent Protein ... Certain cyclases are also activated by Ca(2+)-calmodulin, while some are inhibited by the alpha subunits of the three Gi ... Publication types * Review MeSH terms * Adenylyl Cyclases / chemistry * Adenylyl Cyclases / genetics * Adenylyl Cyclases / ...
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. ...
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 (-) ...
... or c-Src activation with subsequent activation of MAPK or calcium calmodulin-dependent kinases [11, 12]. The extent to which E2 ... G-proteins, protein kinase B (PKB)/PI3K, and protein kinase C (PKC). Moreover, E2 also signals nongenomically via GPER. This ... E. L. Ding, Y. Song, J. E. Manson et al., "Sex hormone-binding globulin and risk of type 2 diabetes in women and men," The New ... membrane-localized ER with adaptor proteins such as c-Src and downstream rapid signaling via mitogen-activated protein kinase ( ...
Signal transduction was triggered in both species with calcium (and G-proteins in pear) and interconnected hormonal signaling ( ... calmodulin binding proteins (IQD13 and IQD31 in apple; IQD6 in pear), calmodulin dependent protein kinase (CPK) (CPK8 and CPK28 ... Some G-proteins are known to interact with Plant U-box type E3 ubiquitin ligases (PUBs), implicated in the regulation of the ... calcium-dependent protein kinase; DFR, dihydroflavonol reductase; F3H, flavanone 3-hydroxylase; FLS, flavonol synthase; HCT, ...
Calcium-Calmodulin-Dependent Protein Kinase Type 4 100% * Colitis 60% * Calcium(0) 45% ... Calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation contributes to the pathogenesis of experimental colitis via ... Gastric carcinoids: Does type of surgery or tumor affect survival?. Crown, A., Kennecke, H., Kozarek, R., Lopez-Aguiar, A. G., ... Evaluating the Impact of Technique and Mesh Type in Complicated Ventral Hernia Repair: A Prospective Randomized Multicenter ...
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 ...
... type I interferon via N-methyl-d-aspartate receptor activation with Ca2+ influx activating Calcium/calmodulin-dependent protein ... kinase /interferon regulatory factor 354. Indeed, our results are in keeping with the recent finding that the monocyte- ... elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1)) was associated with chest pain, and dyspnea20 up to 8- ... Aceti, A., et al. Serum S100B protein as a marker of severity in Covid-19 patients. Sci Rep 10, 18665 (2020).. ...
... 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 ...
This gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). The CASK ... Genetic Testing Registry: Syndromic X-linked intellectual disability Najm type Genetic and Rare Diseases Information Center. * ... Calcium/calmodulin-dependent serine protein kinase and mental retardation. Ann Neurol. 2009 Oct;66(4):438-43. doi: 10.1002/ana. ... Research suggests that the CASK protein may also interact with the protein produced from another gene, FRMD7, to promote ...
Calcium-Calmodulin-Dependent Protein Kinase Type 2 14% * Excitatory Amino Acids 13% ...
Zou, D. J., Cline, H. T. (October 1999) Postsynaptic calcium/calmodulin-dependent protein kinase II is required to limit ... protein structure, function, modification (13)*protein types (13)*enzymes (13)*kinase (13)*CaMKII (13) ... Part II: mediation by calcium/calmodulin-dependent protein kinase II. Journal of Neuroscience, 18 (17). pp. 6814-21. ISSN 0270- ... Shirke, A. M., Malinow, R. (November 1997) Mechanisms of potentiation by calcium-calmodulin kinase II of postsynaptic ...
purine rich element binding protein B. 14q21. 18405950. 24245. Camk2b. calcium/calmodulin-dependent protein kinase II, beta. ... protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I). 14q22. 18405950. ... kinase insert domain protein receptor. -. 17517326. 64030. Kit. v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog. ... transmembrane emp24 protein transport domain containing 5. 14p22. 17451403. 18405950. 25667. Bmp3. bone morphogenetic protein 3 ...
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. ... Our findings suggest that ς2 receptors are coupled to the DAT via a Ca2+/calmodulin-dependent protein kinase II transduction ... However, two inhibitors of Ca2+/calmodulin-dependent protein kinase II blocked enhancement in AMPH-stimulated release by (+)- ...
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 ...
Ca(2+)-Calmodulin Dependent Protein Kinase. Calcium-Calmodulin-Dependent Protein Kinases. Cholesterol Esterase. Sterol Esterase ... SHP1 Protein Tyrosine Phosphatase. Protein Tyrosine Phosphatase, Non-Receptor Type 6. Thioredoxin Reductase (NADPH). ... Unpublished Works [Publication Type]. Unpublished Works. V03 - Study Characteristics. Case Reports [Publication Type]. Case ... Protein Isoprenylation. Protein Prenylation. G09 - Circulatory and Respiratory Physiology. Hemodynamic Processes. Hemodynamics ...
Ca(2+)-Calmodulin Dependent Protein Kinase. Calcium-Calmodulin-Dependent Protein Kinases. Cholesterol Esterase. Sterol Esterase ... SHP1 Protein Tyrosine Phosphatase. Protein Tyrosine Phosphatase, Non-Receptor Type 6. Thioredoxin Reductase (NADPH). ... Unpublished Works [Publication Type]. Unpublished Works. V03 - Study Characteristics. Case Reports [Publication Type]. Case ... Protein Isoprenylation. Protein Prenylation. G09 - Circulatory and Respiratory Physiology. Hemodynamic Processes. Hemodynamics ...
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 ... albicans and other fungi transmit external stimuli through 2 major protein kinase cascades. These govern multiple functions, ...
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 ... albicans and other fungi transmit external stimuli through 2 major protein kinase cascades. These govern multiple functions, ...
... associated proteins kinase (ZAP70) and activation from the downstream kinase calcium/calmodulin-dependent proteins kinase type ... Furthermore, peripheral T cells from individuals with SLE have altered signaling and a faster T cell calcium flux than those of ... leading to the usage of the adaptor molecule spleen tyrosine kinase (SYK) as opposed to the usual string (TCR) ... serotype 1 (Sp1) constitutes a significant cause of seasonal endemic meningitis in all age groups in the African meningitis ...
... 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 ...
Accumulation of toxic lipids evokes the unfolded protein response (UPR) and apoptotic death of macrophages and vascular cells ... cAMP-dependent protein kinase and Ca2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation ... Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways ... cAMP-dependent protein kinase and Ca2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation ...
... 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 ...
Protein Capture Reagents. *Protein tags. *Skeletal muscle. *Stem cell. *Transcription factors. *Xenopus ...
  • Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly promotes the phosphorylation and synergistic activation of the enzyme by calcium/calmodulin-dependent protein kinase I kinase. (wikipedia.org)
  • Characterization of substrate phosphorylation and use of calmodulin mutants to address implications from the enzyme crystal structure of calmodulin-dependent protein kinase I". J. Biol. (wikipedia.org)
  • The discovery of new isoforms has also revealed unanticipated mechanisms of regulation, including activation or inhibition by the G-protein beta gamma subunit complex, inhibition by G(o) alpha, inhibition by Ca2+, and phosphorylation by protein kinases C and A. The effects of activators are often highly synergistic or conditional, suggesting function of these enyzmes as coincidence detectors. (nih.gov)
  • 1. Erneux C. S Cohen, D L Garbers (1983) The kinetics of tyrosine phosphorylation by the purified epidermal growth factor receptor kinase of A-431 cells. (iribhm.org)
  • 4. Communi, D., Vanweyenberg, V., Erneux, C. D-myo-inositol 1,4,5-trisphosphate 3-kinase-A is activated by receptor activation by a calcium:calmodulin-dependent protein kinase II phosphorylation mechanism EMBO J. 1997 16: 1943-1952. (iribhm.org)
  • and protein serine/threonine kinase activity. (nih.gov)
  • 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)
  • This gene provides instructions for making a protein called calcium/calmodulin-dependent serine protein kinase (CASK). (medlineplus.gov)
  • Under conditions of insufficient energy, AMPK activates upon its binding with AMP or adenosine diphosphate (ADP) [ 1 ] . (encyclopedia.pub)
  • Moreover, CFA-induced sensory nerve growth, which involves the extracellular signal-related kinase (ERK1/2) signaling pathway and likely contributes to inflammation-induced hyperalgesia, was blocked with the Cav2.2 inhibitor. (frontiersin.org)
  • Among the cysteinyl leukotriene receptor 1 antagonists, zafirlukast, pranlukast, and montelukast, only zafirlukast enhanced insulin secretion in a concentration-dependent manner in both low and high glucose conditions and elevated the level of [Ca2+](i), further activating Ca2+/calmodulin-dependent protein kinase II (CaMKII), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) signaling. (unist.ac.kr)
  • Here, we show that endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and that loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. (silverchair.com)
  • The interaction regulates two self-regulatory calcium dependent feedback mechanism, calcium dependent inactivation (CDI), and calcium-dependent facilitation (CDF). (embl.de)
  • Additionally, Xenopus live imaging findings, coupled with studies of cultured Xenopus spinal neurons, demonstrate that an optimal frequency of calcium transients regulates neurite extension ( Gu and Spitzer, 1995 ). (frontiersin.org)
  • These effects were nearly abolished by the L-type Ca2+ channel antagonist nifedipine, while treatment with thapsigargin, a sarco/endoplasmic reticulum Ca2+ ATPase inhibitor, did not have the same effect, suggesting that zafirlukast primarily induces the entry of extracellular Ca2+ rather than intracellular Ca2+ from the endoplasmic reticulum. (unist.ac.kr)
  • Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. (idrblab.net)
  • All of the membrane-bound enzymes are activated by the alpha subunit of G alpha, a receptor-regulated, heterotrimeric guanine nucleotide-binding protein, and by the diterpene forskolin. (nih.gov)
  • 2. Takazawa K., Vandekerckhove J., Dumont J.E. and Erneux C. (1990) Cloning and expression in Escherichia coli of a rat brain cDNA encoding a Ca2+/calmodulin-sensitive inol 1,4,5-trisphosphate 3-kinase. (iribhm.org)
  • 3. Verjans B., Desmedt F., Lecocq R., Vanweyenberg V., Moreau C., Erneux C. Cloning and expression in Escherichia coli of a dog thyroid cDNA encoding an inositol 1,4,5-trisphosphate 5-phosphatase. (iribhm.org)
  • Our interest in the PI metabolism started with the cloning of a series of inositol polyphosphate 5-phosphatase and Ins(1,4,5)P3 3-kinases (the enzymes that phosphorylate Ins(1,4,5)P3 to Ins(1,3,4,5)P4). (iribhm.org)
  • Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. (mdpi.com)
  • Lead absorption is augmented in the presence of iron, zinc, and calcium deficiency. (medscape.com)
  • Additionally, the reduction in the effect of (+)-pentazocine by the inclusion of ethylene glycol bis(β-aminoethyl ether)- N,N,N′,N′ -tetraacetic acid led us to hypothesize that ς 2 receptor activation initiated a Ca 2+ -dependent process that resulted in enhancing the outward flow of DA via the DAT. (aspetjournals.org)
  • Calcium/calmodulin-dependent protein kinase type 1 is an enzyme that in humans is encoded by the CAMK1 gene. (wikipedia.org)
  • Entrez Gene: CAMK1 calcium/calmodulin-dependent protein kinase I". Bredt DS, Ferris CD, Snyder SH (1992). (wikipedia.org)
  • Expression of each cluster's gene signatures was validated using multiplex fluorescence in situ hybridization (FISH) co-stained with piwi-1 and largely confirmed the cell clusters revealed by scRNA-seq. (stowers.org)
  • Cancerous cells adopt various strategies to evade anoikis, for instance, anti-apoptotic BCL-2 protein activation, adhesion-related gene silence, focal adhesion kinase signaling perturbation, epithelial-to-mesenchymal transition induction, and others [ 4 ]. (biomedcentral.com)
  • Formation of stable, late phase HFS-LTP requires mRNA synthesis and is coupled to upregulation of the immediate early gene activity-regulated cytoskeleton-associated protein (Arc). (jneurosci.org)
  • Research suggests that the CASK protein may also interact with the protein produced from another gene, FRMD7 , to promote development of the nerves that control eye movement (the oculomotor neural network). (medlineplus.gov)
  • Mutations in the CASK gene affect the role of the CASK protein in brain development and function, resulting in the signs and symptoms of CASK -related intellectual disability. (medlineplus.gov)
  • Affected individuals with nystagmus may have CASK gene mutations that disrupt the interaction between the CASK protein and the protein produced from the FRMD7 gene, leading to problems with the development of the oculomotor neural network and resulting in abnormal eye movements. (medlineplus.gov)
  • Insights into voltage-gated calcium channel regulation from the structureof the CaV1.2 IQ domain-Ca2+/calmodulin complex. (embl.de)
  • The pre-miR-148/152 family members have a stem-loop structure (Figure 1 ) that is processed into the mature members of the miR-148/152 family by a series of intranuclear and intracytoplasmic enzymes. (biomedcentral.com)
  • Severe cases (cases that require hospitalization) are at risk for both indirect and direct mechanisms of COVID-19 associated brain damage, particularly from hypoxia 5 , 6 , stroke, as well as the immune and inflammatory response to SARS-CoV-2 1 . (medrxiv.org)
  • The plethora of receptors, G proteins, and adenylyl cyclases permits assembly of very complex signaling systems with a wide variety of integrative characteristics. (nih.gov)
  • E2 mediates its effects via 3 receptors-E2 receptor α (ER α ), E2 receptor β (ER β ), and the newly described G protein-coupled E2 receptor 1 (GPER). (hindawi.com)
  • Our findings suggest that ς 2 receptors are coupled to the DAT via a Ca 2+ /calmodulin-dependent protein kinase II transduction system in PC12 cells, and that ς 2 receptor antagonists might be useful in the treatment of drug abuse by blocking elevation of DA levels via reversal of the DAT. (aspetjournals.org)
  • 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)
  • It consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans. (encyclopedia.pub)
  • The isoleucine-glutamine (IQ) motif in the voltage gated calcium channel IQ domain interacts with hydrophobic pockets of Ca2+/calmodulin ( PUBMED:16299511 ). (embl.de)
  • 5. Pesesse, X., Deleu, S., De Smedt, F., Drayer L.A. , Erneux C. (1997) Identification of a second SH2-domain-containing protein closely related to the phosphatidylinositol polyphosphate 5-phosphatase SHIP. (iribhm.org)
  • Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. (embl.de)
  • 2007). Moreover, the phosphoinositide (PI) 3-kinase (PI3K) pathway is one of the most frequently mutated signaling pathways in cancer being actively pursued today as a therapeutic target. (iribhm.org)
  • The CASK protein is primarily found in nerve cells (neurons) in the brain, where it helps control the activity (expression) of other genes that are involved in brain development. (medlineplus.gov)
  • Calcium-evoked dendritic exocytosis in cultured hippocampal neurons. (cshl.edu)
  • 1998). "Components of a calmodulin-dependent protein kinase cascade. (wikipedia.org)
  • Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. (idrblab.net)
  • The coronavirus genome encodes a spike protein, an envelope protein, a membrane protein, and a nucleoprotein. (creative-biolabs.com)
  • Orthologous to human CAMK2A (calcium/calmodulin dependent protein kinase II alpha). (nih.gov)
  • Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. (idrblab.net)
  • A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs ( Brief Bioinform, 21: 649-662, 2020 ). (idrblab.net)
  • Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. (idrblab.net)
  • The elimination half-life of lead in adult human blood has been estimated to be 1 month, whereas in children it may be as high as 10 months. (medscape.com)
  • Calcium/calmodulin-Dependent Protein Kinase II Inhibitor 1 (aa 1-78) Protein, tagged with His tag. (creative-biolabs.com)
  • Local infusion of the transcription inhibitor actinomycin D (ACD) 1 hr before or immediately before BDNF infusion inhibited BDNF-LTP and upregulation of Arc protein expression. (jneurosci.org)
  • Changes in activity-dependent calcium flux through voltage-gated calciumchannels (Ca(V)s) drive two self-regulatory calcium-dependent feedbackprocesses that require interaction between Ca(2+)/calmodulin (Ca(2+)/CaM)and a Ca(V) channel consensus isoleucine-glutamine (IQ) motif:calcium-dependent inactivation (CDI) and calcium-dependent facilitation(CDF). (embl.de)
  • ACD applied 2 hr after BDNF infusion had no effect, defining a critical time window of transcription-dependent synaptic strengthening. (jneurosci.org)
  • The results strongly support a role for BDNF in triggering transcription-dependent, late phase LTP in the intact adult brain. (jneurosci.org)
  • On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels. (embl.de)
  • Release of this repression results in activation of multiple effector pathways, including Runx2- and β-catenin-dependent pathways. (silverchair.com)
  • [ 1 ] These therapies have improved the survival of transplanted organs. (medscape.com)
  • Our investigation reveals that darovasertib potently inhibits PKC as well as PKN/PRK, an AGC kinase family that is part of the "dark kinome. (bvsalud.org)
  • It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 in yeast, and SnRK1 in plants. (encyclopedia.pub)
  • these proteins now comprise a family of at least 10. (nih.gov)
  • 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)
  • Metabolomics analysis revealed significant alteration in the intracellular levels of six (oxalic acid, cholesterol, 1-ethylpyrrolidine, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, β-alanine, and putrescine) among all 37 identified metabolites during 7 days without anchorage. (biomedcentral.com)
  • Together these changes increase the risk of nonalcoholic steatohepatitis, type 2 diabetes, and cardiovascular disease and its complications [ 1 ]. (hindawi.com)
  • Among them, spike protein is the most important surface membrane protein of coronavirus. (creative-biolabs.com)
  • Voltage gated calcium channels control cellular calcium entry in response to changes in membrane potential. (embl.de)
  • 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)
  • The severe form of this disorder, MICPCH, is caused by mutations that eliminate CASK function, while mutations that impair the function of this protein cause the milder form, XL-ID with or without nystagmus. (medlineplus.gov)
  • Methods: We examined ZTR-induced cell death, mitochondrial dysfunction, and biogenesis defect at RNA, protein, and cellular levels. (bvsalud.org)
  • Lead absorption is dependent on several factors, including the physical form of lead, the particle size ingested, the GI transit time, and the nutritional status of the person ingesting. (medscape.com)
  • Voltage-gated calcium channels (VGCCs) are important mediators of pain hypersensitivity during inflammatory states, but their role in sensory nerve growth remains underexplored. (frontiersin.org)
  • Certain cyclases are also activated by Ca(2+)-calmodulin, while some are inhibited by the alpha subunits of the three Gi proteins. (nih.gov)
  • We isolated X1 neoblasts cells enriched in high piwi-1 expression (Neoblast Population), and profiled ∼7,614 individual cells via scRNA-seq. (stowers.org)
  • Our study demonstrated that prolonging the anchorage-free lifetime of non-small-cell lung cancer NCI-H460 cells for 7 days strengthened anoikis resistance, as shown by higher half-life and capability to survive and grow without anchorage, compared to wild-type cells or those losing anchorage for 3 days. (biomedcentral.com)
  • Blue cells = expressed in wild-type. (jax.org)