rho Guanine Nucleotide Dissociation Inhibitor alpha
Guanine Nucleotide Dissociation Inhibitors
rho-Specific Guanine Nucleotide Dissociation Inhibitors
rho Guanine Nucleotide Dissociation Inhibitor gamma
rho Guanine Nucleotide Dissociation Inhibitor beta
Rho Guanine Nucleotide Exchange Factors
Guanine Nucleotide Exchange Factors
rho GTP-Binding Proteins
Guanosine Diphosphate
rhoA GTP-Binding Protein
cdc42 GTP-Binding Protein
Guanosine Triphosphate
GTP-Binding Protein alpha Subunits, Gi-Go
GTP-Binding Proteins
ral Guanine Nucleotide Exchange Factor
Protein Binding
rap GTP-Binding Proteins
ral GTP-Binding Proteins
Guanine Nucleotides
alpha-Macroglobulins
alpha 1-Antitrypsin
Amino Acid Sequence
Molecular Sequence Data
GTP-Binding Protein alpha Subunits, G12-G13
Guanosine 5'-O-(3-Thiotriphosphate)
A Kinase Anchor Proteins
Guanine
alpha-2-Antiplasmin
rho-Associated Kinases
Signal Transduction
alpha 1-Antichymotrypsin
Protein Structure, Tertiary
rac1 GTP-Binding Protein
Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. (1/73)
The Rho small G protein family members regulate various actin cytoskeleton-dependent cell functions. The Rho GDI (GDP dissociation inhibitor) family, consisting of Rho GDIalpha, -beta, and -gamma, is a regulator that keeps the Rho family members in the cytosol as the GDP-bound inactive form and translocates the GDP-bound form from the membranes to the cytosol after the GTP-bound form accomplishes their functions. Rho GDIalpha is ubiquitously expressed in mouse tissues and shows GDI activity on all the Rho family members in vitro. We have generated mice lacking Rho GDIalpha by homologous recombination to clarify its in vivo function. Rho GDIalpha -/- mice showed several abnormal phenotypes. Firstly, Rho GDIalpha -/- mice were initially viable but developed massive proteinuria mimicking nephrotic syndrome, leading to death due to renal failure within a year. Histologically, degeneration of tubular epithelial cells and dilatation of distal and collecting tubules were readily detected in the kidneys. Secondly, Rho GDIalpha -/- male mice were infertile and showed impaired spermatogenesis with vacuolar degeneration of seminiferous tubules in their testes. Thirdly, Rho GDIalpha -/- embryos derived from Rho GDIalpha -/- female mice were defective in the postimplantation development. In addition, these morphological and functional abnormalities showed age-dependent progression. These results suggest that the signaling pathways of the Rho family members regulated by Rho GDIalpha play important roles in maintaining the structure and physiological function of at least kidneys and reproductive systems in adult mice. (+info)Mapping the binding site for the GTP-binding protein Rac-1 on its inhibitor RhoGDI-1. (2/73)
BACKGROUND: Members of the Rho family of small GTP-binding proteins, such as Rho, Rac and Cdc42, have a role in a wide range of cell responses. These proteins function as molecular switches by virtue of a conformational change between the GTP-bound (active) and GDP-bound (inactive) forms. In addition, most members of the Rho and Rac subfamilies cycle between the cytosol and membrane. The cytosolic guanine nucleotide dissociation inhibitors, RhoGDIs, regulate both the GDP/GTP exchange cycle and the membrane association/dissociation cycle. RESULTS: We have used NMR spectroscopy and site-directed mutagenesis to identify the regions of human RhoGDI-1 that are involved in binding Rac-1. The results emphasise the importance of the flexible regions of both proteins in the interaction. At least one specific region (residues 46-57) of the flexible N-terminal domain of RhoGDI, which has a tendency to form an amphipathic helix in the free protein, makes a major contribution to the binding energy of the complex. In addition, the primary site of Rac-1 binding on the folded domain of RhoGDI involves the beta4-beta5 and beta6-beta7 loops, with a slight movement of the 3(10) helix accompanying the interaction. This binding site is on the same face of the protein as the binding site for the isoprenyl group of post-translationally modified Rac-1, but is distinct from this site. CONCLUSIONS: Isoprenylated Rac-1 appears to interact with three distinct sites on RhoGDI. The isoprenyl group attached to the C terminus of Rac-1 binds in a pocket in the folded domain of RhoGDI. This is distinct from the major site on this domain occupied by Rac-1 itself, which involves two loops at the opposite end to the isoprenyl-binding site. It is probable that the flexible C-terminal region of Rac-1 extends from the site at which Rac-1 contacts the folded domain of RhoGDI to allow the isoprenyl group to bind in the pocket at the other end of the RhoGDI molecule. Finally, the flexible N terminus of RhoGDI-1, and particularly residues 48-58, makes a specific interaction with Rac-1 which contributes substantially to the binding affinity. (+info)Unique in vivo associations with SmgGDS and RhoGDI and different guanine nucleotide exchange activities exhibited by RhoA, dominant negative RhoA(Asn-19), and activated RhoA(Val-14). (3/73)
We compared the in vivo characteristics of hemagglutinin (HA)-tagged RhoA, dominant negative RhoA(Asn-19), and activated RhoA(Val-14) stably expressed in Chinese hamster ovary (CHO) cells. Proteins co-precipitating with these HA-tagged GTPases were identified by peptide sequencing or by Western blotting. Dominant negative RhoA(Asn-19) co-precipitates with the guanine nucleotide exchange factor (GEF) SmgGDS but does not detectably interact with other expressed GEFs, such as Ost or Dbl. SmgGDS co-precipitates minimally with wild-type RhoA and does not detectably associate with RhoA(Val-14). The guanine nucleotide dissociation inhibitor RhoGDI co-precipitates with RhoA, and to a lesser extent with RhoA(Val-14), but does not detectably co-precipitate with RhoA(Asn-19). Wild-type RhoA is predominantly in the [(32)P]GDP-bound form, RhoA(Val-14) is predominantly in the [(32)P]GTP-bound form, and negligible levels of [(32)P]GDP or [(32)P]GTP are bound to RhoA(Asn-19) in (32)P-labeled cells. Immunofluorescence analyses indicate that HA-RhoA(Asn-19) is excluded from the nucleus and cell junctions. Microinjection of SmgGDS cDNA into CHO cells stably expressing HA-RhoA causes HA-RhoA to be excluded from the nucleus and cell junctions, similar to the distribution of RhoA(Asn-19). Our findings indicate that the expression of RhoA(Asn-19) may specifically inhibit signaling pathways that rely upon the SmgGDS-dependent activation of RhoA. (+info)Human RhoA/RhoGDI complex expressed in yeast: GTP exchange is sufficient for translocation of RhoA to liposomes. (4/73)
The human small GTPase, RhoA, expressed in Saccharomyces cerevisiae is post-translationally processed and, when co-expressed with its cytosolic inhibitory protein, RhoGDI, spontaneously forms a heterodimer in vivo. The RhoA/RhoGDI complex, purified to greater than 98% at high yield from the yeast cytosolic fraction, could be stoichiometrically ADP-ribosylated by Clostridium botulinum C3 exoenzyme, contained stoichiometric GDP, and could be nucleotide exchanged fully with [3H]GDP or partially with GTP in the presence of submicromolar Mg2+. The GTP-RhoA/RhoGDI complex hydrolyzed GTP with a rate constant of 4.5 X 10(-5) s(-1), considerably slower than free RhoA. Hydrolysis followed pseudo-first-order kinetics indicating that the RhoA hydrolyzing GTP was RhoGDI associated. The constitutively active G14V-RhoA mutant expressed as a complex with RhoGDI and purified without added nucleotide also bound stoichiometric guanine nucleotide: 95% contained GDP and 5% GTP. Microinjection of the GTP-bound G14V-RhoA/RhoGDI complex (but not the GDP form) into serum-starved Swiss 3T3 cells elicited formation of stress fibers and focal adhesions. In vitro, GTP-bound-RhoA spontaneously translocated from its complex with RhoGDI to liposomes, whereas GDP-RhoA did not. These results show that GTP-triggered translocation of RhoA from RhoGDI to a membrane, where it carries out its signaling function, is an intrinsic property of the RhoA/RhoGDI complex that does not require other protein factors or membrane receptors. (+info)Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia. (5/73)
Severe congenital neutropenia (SCN) or Kostmann syndrome is a disorder of myelopoiesis characterized by a maturation arrest at the stage of promyelocytes or myelocytes in bone marrow and absolute neutrophil counts less than 200/microL in peripheral blood. Treatment of these patients with granulocyte colony-stimulating factor (G-CSF) leads to a significant increase in circulating neutrophils and a reduction in infection-related events in more than 95% of the patients. To date, little is known regarding the underlying pathomechanism of SCN. G-CSF-induced neutrophils of patients with SCN are functionally defective (eg, chemotaxis, superoxide anion generation, Ca(++ )mobilization). Two guanosine triphosphatases (GTPases), Rac2 and RhoA, were described to be involved in many neutrophil functions. The expression of these GTPases and their regulation in patients' neutrophils were of interest. This study determined that the guanosine diphosphate (GDP)-dissociation inhibitor RhoGDI is overexpressed at the protein level in patients' neutrophils and that overexpression is a result of G-CSF treatment. RhoA and LyGDI are expressed at similar levels, whereas Rac2 shows a decreased expression. In addition, association of Rac2 and RhoGDI or LyGDI is abrogated or not detectable based on the low Rac2 expression in patients' neutrophils. (Blood. 2000;95:2947-2953) (+info)Rho family GTPase Cdc42 is essential for the actin-based motility of Shigella in mammalian cells. (6/73)
Shigella, the causative agent of bacillary dysentery, is capable of directing its movement within host cells by exploiting actin dynamics. The VirG protein expressed at one pole of the bacterium can recruit neural Wiskott-Aldrich syndrome protein (N-WASP), a downstream effector of Cdc42. Here, we show that Cdc42 is required for the actin-based motility of Shigella. Microinjection of a dominant active mutant Cdc42, but not Rac1 or RhoA, into Swiss 3T3 cells accelerated Shigella motility. In add-back experiments in Xenopus egg extracts, addition of a guanine nucleotide dissociation inhibitor for the Rho family, RhoGDI, greatly diminished the bacterial motility or actin assembly, which was restored by adding activated Cdc42. In N-WASP-depleted extracts, the bacterial movement almost arrested was restored by adding exogenous N-WASP but not H208D, an N-WASP mutant defective in binding to Cdc42. In pyrene actin assay, Cdc42 enhanced VirG-stimulating actin polymerization by N-WASP-actin-related protein (Arp)2/3 complex. Actually, Cdc42 stimulated actin cloud formation on the surface of bacteria expressing VirG in a solution containing N-WASP, Arp2/3 complex, and G-actin. Immunohistological study of Shigella-infected cells expressing green fluorescent protein-tagged Cdc42 revealed that Cdc42 accumulated by being colocalized with actin cloud at one pole of intracellular bacterium. Furthermore, overexpression of H208D mutant in cells interfered with the actin assembly of infected Shigella and diminished the intra- and intercellular spreading. These results suggest that Cdc42 activity is involved in initiating actin nucleation mediated by VirG-N-WASP-Arp2/3 complex formed on intracellular Shigella. (+info)RhoGDI-binding-defective mutant of Cdc42Hs targets to membranes and activates filopodia formation but does not cycle with the cytosol of mammalian cells. (7/73)
We have identified a mutant of the human G-protein Cdc42Hs, R66E, that fails to form a detectable complex with the GDP-dissociation inhibitor RhoGDI in cell-free systems or in intact cells. This point mutant is prenylated, binds guanine nucleotide and interacts with GTPase-activating protein in a manner indistinguishable from wild-type Cdc42Hs. Immunofluorescence localization studies revealed that this RhoGDI-binding-defective mutant is found predominantly in the Golgi apparatus, with a staining pattern similar to that of the wild-type protein. However, unlike wild-type Cdc42Hs, which is distributed in both the microsomal membrane and cytosolic fractions, studies using differential centrifugation show that prenylated R66E Cdc42Hs is found exclusively in association with lipid bilayers. Additionally, whereas the overexpression of RhoGDI results in an apparent translocation of wild-type Cdc42Hs from the Golgi apparatus into the cytosol, identical RhoGDI-overexpression conditions do not alter the Golgi localization of the R66E mutant. Furthermore, overexpression of this RhoGDI-binding-defective mutant of Cdc42Hs seems to activate redistribution of the actin cytoskeleton and filopodia formation in fibroblasts in a manner indistinguishable from the wild-type protein. Taken together, these results suggest that the interaction of Cdc42Hs with RhoGDI is not essential for proper membrane targeting of nascent prenylated Cdc42Hs in mammalian cells; neither is this interaction an essential part of the mechanism by which Cdc42Hs activates filopodia formation. However, it does seem that redistribution of Cdc42Hs to the cytosolic compartment is absolutely dependent on RhoGDI interaction. (+info)Inhibition of Rho family GTPases by Rho GDP dissociation inhibitor disrupts cardiac morphogenesis and inhibits cardiomyocyte proliferation. (8/73)
Studies of Rho GTPases in Drosophila and Xenopus suggest that Rho family proteins may play an important role in embryogenesis. A reverse genetic approach was employed to explore the role of Rho GTPases in murine cardiac development. Cardiac-specific inhibition of Rho family protein activities was achieved by expressing Rho GDIalpha, a specific GDP dissociation inhibitor for Rho family proteins, using the alpha-myosin heavy chain promoter, active at embryonic day (E)8.0 during morphogenesis of the linear heart tube. RhoA, Rac1 and Cdc42 activities were significantly inhibited, as shown by decreased membrane translocation of these proteins in the transgenic hearts. Transgenic F1 mice for each of two independent lines expressing the highest levels of the transgene, died around E10.5. Homozygotes of the middle copy-number lines, in which Rho GDIalpha expression was increased four-fold over normal levels, were also embryonic lethal. Cardiac morphogenesis in these embryos was disrupted, with incomplete looping, lack of chamber demarcation, hypocellularity and lack of trabeculation. Cell proliferation was inhibited in the transgenic hearts, as shown by immunostaining with anti-phosphohistone H3, a marker of mitosis. In addition, ventricular hypoplasia was associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases, and with down-regulation of cyclin A, while cell survival was not affected. These results reveal new biological functions for Rho family proteins as essential determinants of cell proliferation signals at looping and chamber maturation stages in mammalian cardiac development. (+info)Rho Guanine Nucleotide Dissociation Inhibitor alpha (RhoGDIα) is a protein that regulates the Rho family of small GTPases, which are important signaling molecules involved in various cellular processes such as actin cytoskeleton regulation, cell motility, and gene expression.
RhoGDIα functions by binding to and inhibiting the dissociation of GDP from Rho GTPases, thereby keeping them in an inactive state in the cytoplasm. When a signal is received, RhoGDIα releases the Rho GTPase, allowing it to exchange GDP for GTP and become activated. Once activated, the Rho GTPase can then interact with downstream effectors to carry out its functions.
RhoGDIα has been implicated in various physiological and pathological processes, including cancer, inflammation, and neurological disorders.
Guanine Nucleotide Dissociation Inhibitors (GDI) are a group of proteins that bind to and inhibit the dissociation of guanine nucleotides from small GTPases, which are important regulatory molecules involved in various cellular processes such as signal transduction, vesicle trafficking, and cytoskeleton organization.
GDI's function is to maintain these small GTPases in their inactive state by keeping them bound to guanine nucleotides, specifically GDP (guanosine diphosphate). By doing so, GDIs help regulate the activity of small GTPases and control their subcellular localization.
GDIs have been identified in various organisms, including bacteria, yeast, and mammals. In humans, there are two major types of GDIs: RhoGDI (also known as D4-GDI) and RacGDI (also known as GDI-α). These GDIs play crucial roles in regulating the activity of Rho family GTPases, which are involved in various cellular functions such as cell motility, membrane trafficking, and gene expression.
Overall, Guanine Nucleotide Dissociation Inhibitors are essential regulators of small GTPases, controlling their activity and localization to ensure proper cellular function.
Rho-specific guanine nucleotide dissociation inhibitors (RhoGDI) are a group of proteins that regulate the function of Rho GTPases, which are important signaling molecules involved in various cellular processes such as actin cytoskeleton regulation, gene expression, and cell cycle progression.
RhoGDIs bind to Rho GTPases in their inactive state, preventing them from interacting with guanine nucleotide exchange factors (GEFs) that would activate them. By doing so, RhoGDIs help regulate the spatial and temporal activation of Rho GTPases, ensuring that they are activated only when and where needed in the cell.
RhoGDI proteins have been identified as potential targets for therapeutic intervention in various diseases, including cancer, inflammation, and neurological disorders. Inhibitors of RhoGDI function have been shown to disrupt Rho GTPase signaling and may have therapeutic benefits in these conditions.
Rho Guanine Nucleotide Dissociation Inhibitor gamma (Rho-GDIγ) is a protein that regulates the Rho family of small GTPases, which are important signaling molecules involved in various cellular processes such as cytoskeleton regulation, cell motility, and gene expression.
Rho-GDIγ functions by binding to and sequestering Rho GTPases in their inactive GDP-bound state in the cytoplasm, preventing them from interacting with downstream effectors. This helps regulate the spatial and temporal activation of Rho GTPases, ensuring proper signal transduction and cellular responses.
Rho-GDIγ is also known as Rho-GDI3 or Ly-GDI, and it shares structural and functional similarities with other Rho-GDI proteins (Rho-GDIα and Rho-GDIβ). However, Rho-GDIγ has a unique pattern of tissue expression and may have distinct regulatory functions in certain cell types.
Rho Guanine Nucleotide Dissociation Inhibitor beta (RhoGDIβ) is a protein that regulates the Rho family of small GTPases, which are important signaling molecules involved in various cellular processes such as actin cytoskeleton regulation, cell motility, and gene expression.
RhoGDIβ functions by binding to and inhibiting the dissociation of GDP from Rho GTPases, thereby keeping them in an inactive state in the cytoplasm. When a signal is received, RhoGDIβ releases the Rho GTPase, allowing it to bind to GTP and become activated. Activated Rho GTPases then interact with downstream effectors to regulate various cellular responses.
RhoGDIβ has been found to play a role in several diseases, including cancer, where it can contribute to tumor progression by promoting cell migration and invasion. Therefore, RhoGDIβ is an attractive target for the development of new therapies for cancer and other diseases.
Rho Guanine Nucleotide Exchange Factors (Rho-GEFs) are a group of proteins that play a crucial role in the regulation of intracellular signaling pathways. They function as molecular switches that activate Rho GTPases, which are important regulators of various cellular processes such as cytoskeleton reorganization, gene expression, cell cycle progression, and cell migration.
Rho-GEFs catalyze the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on Rho GTPases, leading to their activation. This process is tightly regulated and occurs in response to various extracellular signals, such as hormones, growth factors, and integrin-mediated adhesion. Once activated, Rho GTPases interact with downstream effectors to modulate cell behavior.
There are several families of Rho-GEFs, including the Dbl family, the Vav family, and the Trio family, among others. Each family has distinct structural features and regulatory mechanisms that allow for specificity in Rho GTPase activation and downstream signaling. Dysregulation of Rho-GEFs and Rho GTPases has been implicated in various human diseases, including cancer, neurological disorders, and cardiovascular disease.
Guanine Nucleotide Exchange Factors (GEFs) are a group of regulatory proteins that play a crucial role in the activation of GTPases, which are enzymes that regulate various cellular processes such as signal transduction, cytoskeleton reorganization, and vesicle trafficking.
GEFs function by promoting the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on GTPases. GTP is the active form of the GTPase, and its binding to the GTPase leads to a conformational change that activates the enzyme's function.
In the absence of GEFs, GTPases remain in their inactive GDP-bound state, and cellular signaling pathways are not activated. Therefore, GEFs play a critical role in regulating the activity of GTPases and ensuring proper signal transduction in cells.
There are many different GEFs that are specific to various GTPase families, including Ras, Rho, and Arf families. Dysregulation of GEFs has been implicated in various diseases, including cancer and neurological disorders.
Rho GTP-binding proteins are a subfamily of the Ras superfamily of small GTPases, which function as molecular switches in various cellular signaling pathways. These proteins play crucial roles in regulating diverse cellular processes such as actin cytoskeleton dynamics, gene expression, cell cycle progression, and cell migration.
Rho GTP-binding proteins cycle between an active GTP-bound state and an inactive GDP-bound state. In the active state, they interact with various downstream effectors to regulate their respective cellular functions. Guanine nucleotide exchange factors (GEFs) activate Rho GTP-binding proteins by promoting the exchange of GDP for GTP, while GTPase-activating proteins (GAPs) inactivate them by enhancing their intrinsic GTP hydrolysis activity.
There are several members of the Rho GTP-binding protein family, including RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, Cdc42, and Rnd proteins, each with distinct functions and downstream effectors. Dysregulation of Rho GTP-binding proteins has been implicated in various human diseases, including cancer, cardiovascular disease, neurological disorders, and inflammatory diseases.
Guanosine diphosphate (GDP) is a nucleotide that consists of a guanine base, a sugar molecule called ribose, and two phosphate groups. It is an ester of pyrophosphoric acid with the hydroxy group of the ribose sugar at the 5' position. GDP plays a crucial role as a secondary messenger in intracellular signaling pathways and also serves as an important intermediate in the synthesis of various biomolecules, such as proteins and polysaccharides.
In cells, GDP is formed from the hydrolysis of guanosine triphosphate (GTP) by enzymes called GTPases, which convert GTP to GDP and release energy that can be used to power various cellular processes. The conversion of GDP back to GTP can be facilitated by nucleotide diphosphate kinases, allowing for the recycling of these nucleotides within the cell.
It is important to note that while guanosine diphosphate has a significant role in biochemical processes, it is not typically associated with medical conditions or diseases directly. However, understanding its function and regulation can provide valuable insights into various physiological and pathophysiological mechanisms.
RhoA (Ras Homolog Family Member A) is a small GTPase protein that acts as a molecular switch, cycling between an inactive GDP-bound state and an active GTP-bound state. It plays a crucial role in regulating various cellular processes such as actin cytoskeleton organization, gene expression, cell cycle progression, and cell migration.
RhoA GTP-binding protein becomes activated when it binds to GTP, and this activation leads to the recruitment of downstream effectors that mediate its functions. The activity of RhoA is tightly regulated by several proteins, including guanine nucleotide exchange factors (GEFs) that promote the exchange of GDP for GTP, GTPase-activating proteins (GAPs) that stimulate the intrinsic GTPase activity of RhoA to hydrolyze GTP to GDP and return it to an inactive state, and guanine nucleotide dissociation inhibitors (GDIs) that sequester RhoA in the cytoplasm and prevent its association with the membrane.
Mutations or dysregulation of RhoA GTP-binding protein have been implicated in various human diseases, including cancer, neurological disorders, and cardiovascular diseases.
CDC42 is a small GTP-binding protein that belongs to the Rho family of GTPases. It acts as a molecular switch, cycling between an inactive GDP-bound state and an active GTP-bound state, and plays a critical role in regulating various cellular processes, including actin cytoskeleton organization, cell polarity, and membrane trafficking.
When CDC42 is activated by Guanine nucleotide exchange factors (GEFs), it interacts with downstream effectors to modulate the assembly of actin filaments and the formation of membrane protrusions, such as lamellipodia and filopodia. These cellular structures are essential for cell migration, adhesion, and morphogenesis.
CDC42 also plays a role in intracellular signaling pathways that regulate gene expression, cell cycle progression, and apoptosis. Dysregulation of CDC42 has been implicated in various human diseases, including cancer, neurodegenerative disorders, and immune disorders.
In summary, CDC42 is a crucial GTP-binding protein involved in regulating multiple cellular processes, and its dysfunction can contribute to the development of several pathological conditions.
Guanosine triphosphate (GTP) is a nucleotide that plays a crucial role in various cellular processes, such as protein synthesis, signal transduction, and regulation of enzymatic activities. It serves as an energy currency, similar to adenosine triphosphate (ATP), and undergoes hydrolysis to guanosine diphosphate (GDP) or guanosine monophosphate (GMP) to release energy required for these processes. GTP is also a precursor for the synthesis of other essential molecules, including RNA and certain signaling proteins. Additionally, it acts as a molecular switch in many intracellular signaling pathways by binding and activating specific GTPase proteins.
GTP-binding protein alpha subunits, Gi-Go, are a type of heterotrimeric G proteins that play a crucial role in signal transduction pathways associated with many hormones and neurotransmitters. These G proteins are composed of three subunits: alpha, beta, and gamma. The "Gi-Go" specifically refers to the alpha subunit of these G proteins, which can exist in two isoforms, Gi and Go.
When a G protein-coupled receptor (GPCR) is activated by an agonist, it undergoes a conformational change that allows it to act as a guanine nucleotide exchange factor (GEF). The GEF activity of the GPCR promotes the exchange of GDP for GTP on the alpha subunit of the heterotrimeric G protein. Once GTP is bound, the alpha subunit dissociates from the beta-gamma dimer and can then interact with downstream effectors to modulate various cellular responses.
The Gi-Go alpha subunits are inhibitory in nature, meaning that they typically inhibit the activity of adenylyl cyclase, an enzyme responsible for converting ATP to cAMP. This reduction in cAMP levels can have downstream effects on various cellular processes, such as gene transcription, ion channel regulation, and metabolic pathways.
In summary, GTP-binding protein alpha subunits, Gi-Go, are heterotrimeric G proteins that play an essential role in signal transduction pathways by modulating adenylyl cyclase activity upon GPCR activation, ultimately influencing various cellular responses through cAMP regulation.
GTP-binding proteins, also known as G proteins, are a family of molecular switches present in many organisms, including humans. They play a crucial role in signal transduction pathways, particularly those involved in cellular responses to external stimuli such as hormones, neurotransmitters, and sensory signals like light and odorants.
G proteins are composed of three subunits: α, β, and γ. The α-subunit binds GTP (guanosine triphosphate) and acts as the active component of the complex. When a G protein-coupled receptor (GPCR) is activated by an external signal, it triggers a conformational change in the associated G protein, allowing the α-subunit to exchange GDP (guanosine diphosphate) for GTP. This activation leads to dissociation of the G protein complex into the GTP-bound α-subunit and the βγ-subunit pair. Both the α-GTP and βγ subunits can then interact with downstream effectors, such as enzymes or ion channels, to propagate and amplify the signal within the cell.
The intrinsic GTPase activity of the α-subunit eventually hydrolyzes the bound GTP to GDP, which leads to re-association of the α and βγ subunits and termination of the signal. This cycle of activation and inactivation makes G proteins versatile signaling elements that can respond quickly and precisely to changing environmental conditions.
Defects in G protein-mediated signaling pathways have been implicated in various diseases, including cancer, neurological disorders, and cardiovascular diseases. Therefore, understanding the function and regulation of GTP-binding proteins is essential for developing targeted therapeutic strategies.
A Ral Guanine Nucleotide Exchange Factor (RalGEF) is a type of enzyme that activates the small GTPase proteins known as Ral by promoting the exchange of GDP for GTP. This activation plays a crucial role in various cellular processes, including cell growth, differentiation, and migration. RalGEFs are often targeted in cancer and other diseases due to their involvement in these important signaling pathways.
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.
Rap GTP-binding proteins, also known as Ras-associated binding (Rab) proteins, are a large family of small GTPases that play crucial roles in regulating intracellular vesicle trafficking and membrane transport. These proteins function as molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state. In the active state, Rab proteins interact with various effector molecules to mediate specific steps in vesicle budding, transport, tethering, and fusion.
Rab proteins are involved in several cellular processes, including exocytosis, endocytosis, phagocytosis, autophagy, and Golgi apparatus function. Each Rab protein has a specific subcellular localization and is responsible for regulating distinct steps in membrane trafficking pathways. Dysregulation of Rab GTPases has been implicated in various human diseases, including cancer, neurodegenerative disorders, and infectious diseases.
In summary, Rap GTP-binding proteins are a family of small GTPases that regulate intracellular vesicle trafficking and membrane transport by functioning as molecular switches in specific steps of these processes.
Ral GTP-binding proteins are a subfamily of the Ras superfamily of small GTPases, which are molecular switches that regulate various cellular processes, including signal transduction, membrane trafficking, and cytoskeleton dynamics. Ral proteins exist in two isoforms, RalA and RalB, which bind to and hydrolyze GTP (guanosine triphosphate) and GDP (guanosine diphosphate).
Ral GTP-binding proteins are activated by guanine nucleotide exchange factors (GEFs), which promote the exchange of GDP for GTP, thereby converting Ral proteins into their active state. Once activated, Ral proteins interact with various downstream effectors to regulate diverse cellular functions, such as cell growth, differentiation, survival, and motility.
Ral GTP-binding proteins have been implicated in several human diseases, including cancer, where they contribute to tumor progression and metastasis by promoting cell invasion, migration, and angiogenesis. Therefore, Ral GTP-binding proteins are considered promising targets for the development of novel anti-cancer therapies.
Guanine nucleotides are molecules that play a crucial role in intracellular signaling, cellular regulation, and various biological processes within cells. They consist of a guanine base, a sugar (ribose or deoxyribose), and one or more phosphate groups. The most common guanine nucleotides are GDP (guanosine diphosphate) and GTP (guanosine triphosphate).
GTP is hydrolyzed to GDP and inorganic phosphate by certain enzymes called GTPases, releasing energy that drives various cellular functions such as protein synthesis, signal transduction, vesicle transport, and cell division. On the other hand, GDP can be rephosphorylated back to GTP by nucleotide diphosphate kinases, allowing for the recycling of these molecules within the cell.
In addition to their role in signaling and regulation, guanine nucleotides also serve as building blocks for RNA (ribonucleic acid) synthesis during transcription, where they pair with cytosine nucleotides via hydrogen bonds to form base pairs in the resulting RNA molecule.
Alpha-macroglobulins are a type of large protein molecule found in blood plasma, which play a crucial role in the human body's immune system. They are called "macro" globulins because of their large size, and "alpha" refers to their electrophoretic mobility, which is a laboratory technique used to separate proteins based on their electrical charge.
Alpha-macroglobulins function as protease inhibitors, which means they help regulate the activity of enzymes called proteases that can break down other proteins in the body. By inhibiting these proteases, alpha-macroglobulins help protect tissues and organs from excessive protein degradation and also help maintain the balance of various biological processes.
One of the most well-known alpha-macroglobulins is alpha-1-antitrypsin, which helps protect the lungs from damage caused by inflammation and protease activity. Deficiencies in this protein have been linked to lung diseases such as emphysema and chronic obstructive pulmonary disease (COPD).
Overall, alpha-macroglobulins are an essential component of the human immune system and play a critical role in maintaining homeostasis and preventing excessive tissue damage.
Alpha 1-antitrypsin (AAT, or α1-antiproteinase, A1AP) is a protein that is primarily produced by the liver and released into the bloodstream. It belongs to a group of proteins called serine protease inhibitors, which help regulate inflammation and protect tissues from damage caused by enzymes involved in the immune response.
Alpha 1-antitrypsin is particularly important for protecting the lungs from damage caused by neutrophil elastase, an enzyme released by white blood cells called neutrophils during inflammation. In the lungs, AAT binds to and inhibits neutrophil elastase, preventing it from degrading the extracellular matrix and damaging lung tissue.
Deficiency in alpha 1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD) and liver disease. The most common cause of AAT deficiency is a genetic mutation that results in abnormal folding and accumulation of the protein within liver cells, leading to reduced levels of functional AAT in the bloodstream. This condition is called alpha 1-antitrypsin deficiency (AATD) and can be inherited in an autosomal codominant manner. Individuals with severe AATD may require augmentation therapy with intravenous infusions of purified human AAT to help prevent lung damage.
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.
GTP (Guanosine Triphosphate) Phosphohydrolases are a group of enzymes that catalyze the hydrolysis of GTP to GDP (Guanosine Diphosphate) and inorganic phosphate. This reaction plays a crucial role in regulating various cellular processes, including signal transduction pathways, protein synthesis, and vesicle trafficking.
The human genome encodes several different types of GTP Phosphohydrolases, such as GTPase-activating proteins (GAPs), GTPase effectors, and G protein-coupled receptors (GPCRs). These enzymes share a common mechanism of action, in which they utilize the energy released from GTP hydrolysis to drive conformational changes that enable them to interact with downstream effector molecules and modulate their activity.
Dysregulation of GTP Phosphohydrolases has been implicated in various human diseases, including cancer, neurodegenerative disorders, and infectious diseases. Therefore, understanding the structure, function, and regulation of these enzymes is essential for developing novel therapeutic strategies to target these conditions.
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.
GTP-binding protein alpha subunits, G12-G13, are a type of heterotrimeric G proteins that play a crucial role in intracellular signaling pathways. These proteins are composed of three subunits: alpha, beta, and gamma. The alpha subunit of G12-G13 proteins is referred to as Gα12 or Gα13 and binds to guanosine triphosphate (GTP) and guanosine diphosphate (GDP).
When a G protein-coupled receptor (GPCR) is activated by an extracellular signal, it catalyzes the exchange of GDP for GTP on the alpha subunit. This leads to a conformational change in the alpha subunit, causing it to dissociate from the beta and gamma subunits and interact with downstream effectors.
Gα12 and Gα13 are unique among the heterotrimeric G proteins because they preferentially activate Rho guanine nucleotide exchange factors (RhoGEFs), which in turn activate Rho GTPases, leading to changes in the actin cytoskeleton and cellular responses such as cell migration, proliferation, and differentiation.
Dysregulation of GTP-binding protein alpha subunits, G12-G13, has been implicated in various diseases, including cancer and neurological disorders.
A kinase anchor protein (AKAP) is a type of scaffolding protein that plays a role in organizing and targeting various signaling molecules within cells. AKAPs are so named because they can bind to and anchor protein kinases, enzymes that add phosphate groups to other proteins, thereby modulating their activity. This allows for the localized regulation of signaling pathways and helps ensure that specific cellular responses occur in the correct location and at the right time. AKAPs can also bind to other signaling molecules, such as phosphatases, ion channels, and second messenger systems, forming large complexes that facilitate efficient communication between different parts of the cell.
There are many different AKAPs identified in various organisms, and they play crucial roles in a wide range of cellular processes, including cell division, signal transduction, and gene expression. Mutations or dysregulation of AKAPs have been implicated in several diseases, including cancer, cardiovascular disease, and neurological disorders. Therefore, understanding the structure, function, and regulation of AKAPs is an important area of research with potential therapeutic implications.
Guanine is not a medical term per se, but it is a biological molecule that plays a crucial role in the body. Guanine is one of the four nucleobases found in the nucleic acids DNA and RNA, along with adenine, cytosine, and thymine (in DNA) or uracil (in RNA). Specifically, guanine pairs with cytosine via hydrogen bonds to form a base pair.
Guanine is a purine derivative, which means it has a double-ring structure. It is formed through the synthesis of simpler molecules in the body and is an essential component of genetic material. Guanine's chemical formula is C5H5N5O.
While guanine itself is not a medical term, abnormalities or mutations in genes that contain guanine nucleotides can lead to various medical conditions, including genetic disorders and cancer.
Alpha-2-antiplasmin (α2AP) is a protein found in the blood plasma that inhibits fibrinolysis, the process by which blood clots are broken down. It does this by irreversibly binding to and inhibiting plasmin, an enzyme that degrades fibrin clots.
Alpha-2-antiplasmin is one of the most important regulators of fibrinolysis, helping to maintain a balance between clot formation and breakdown. Deficiencies or dysfunction in alpha-2-antiplasmin can lead to an increased risk of bleeding due to uncontrolled plasmin activity.
Rho-associated kinases (ROCKs) are serine/threonine kinases that are involved in the regulation of various cellular processes, including actin cytoskeleton organization, cell migration, and gene expression. They are named after their association with the small GTPase RhoA, which activates them upon binding.
ROCKs exist as two isoforms, ROCK1 and ROCK2, which share a high degree of sequence homology and have similar functions. They contain several functional domains, including a kinase domain, a coiled-coil region that mediates protein-protein interactions, and a Rho-binding domain (RBD) that binds to active RhoA.
Once activated by RhoA, ROCKs phosphorylate a variety of downstream targets, including myosin light chain (MLC), LIM kinase (LIMK), and moesin, leading to the regulation of actomyosin contractility, stress fiber formation, and focal adhesion turnover. Dysregulation of ROCK signaling has been implicated in various pathological conditions, such as cancer, cardiovascular diseases, neurological disorders, and fibrosis. Therefore, ROCKs have emerged as promising therapeutic targets for the treatment of these diseases.
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.
Alpha 1-Antichymotrypsin (ACT), also known as Serpin A1, is a protein found in the blood that belongs to the serine protease inhibitor family. It functions to regulate enzymes that break down other proteins in the body. ACT helps to prevent excessive and potentially harmful proteolytic activity, which can contribute to tissue damage and inflammation.
Deficiency or dysfunction of alpha 1-Antichymotrypsin has been associated with several medical conditions, including:
1. Alpha 1-Antichymotrypsin Deficiency: A rare genetic disorder characterized by low levels of ACT in the blood, which can lead to increased risk of developing lung and liver diseases.
2. Alzheimer's Disease: Increased levels of ACT have been found in the brains of individuals with Alzheimer's disease, suggesting a possible role in the pathogenesis of this neurodegenerative disorder.
3. Cancer: Elevated levels of ACT have been observed in various types of cancer, including lung, breast, and prostate cancers, potentially contributing to tumor growth and metastasis.
4. Inflammatory and immune-mediated disorders: Increased ACT levels are associated with several inflammatory conditions, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and vasculitis, suggesting its involvement in the regulation of the immune response.
5. Cardiovascular diseases: Elevated ACT levels have been linked to an increased risk of developing cardiovascular diseases, including atherosclerosis and myocardial infarction (heart attack).
Understanding the role of alpha 1-Antichymotrypsin in various physiological and pathological processes can provide valuable insights into disease mechanisms and potential therapeutic targets.
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.
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.
Rac1 (Ras-related C3 botulinum toxin substrate 1) is a GTP-binding protein, which belongs to the Rho family of small GTPases. These proteins function as molecular switches that regulate various cellular processes such as actin cytoskeleton organization, gene expression, cell proliferation, and differentiation.
Rac1 cycles between an inactive GDP-bound state and an active GTP-bound state. When Rac1 is in its active form (GTP-bound), it interacts with various downstream effectors to modulate the actin cytoskeleton dynamics, cell adhesion, and motility. Activation of Rac1 has been implicated in several cellular responses, including cell migration, membrane ruffling, and filopodia formation.
Rac1 GTP-binding protein plays a crucial role in many physiological processes, such as embryonic development, angiogenesis, and wound healing. However, dysregulation of Rac1 activity has been associated with various pathological conditions, including cancer, inflammation, and neurological disorders.
Small GTPase - Wikipedia
Truncated Isoform Vav3.1 is Highly Expressed in Ovarian Cancer Stem Cells - Medicine Innovates
DeCS 2013 - New terms
DeCS 2013 - New terms
DeCS 2013 - New terms
DeCS 2013 - New terms
DeCS 2013 - New terms
DeCS 2013 - New terms
DeCS 2013 - New terms
Results for cd04129
SZGR2
Sec5
GSE33292 WT VS TCF1 KO DN3 THYMOCYTE UP
RALGDS | Cancer Genetics Web
MH DELETED MN ADDED MN
Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease...
Phosphorylation of Homer3 by Calcium/Calmodulin-Dependent Kinase II Regulates a Coupling State of Its Target Molecules in...
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GSE43955 TH0 VS TGFB IL6 TH17 ACT CD4 TCELL 20H DN
R-Ras subfamily proteins elicit distinct physiologic effects and phosphoproteome alterations in neurofibromin-null MPNST cells ...
Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin | Journal of...
Molecular dissection of PI3Kβ synergistic activation by receptor tyrosine kinases, GβGγ, and Rho-family GTPases
Polyisoprenylated cysteinyl amide inhibitors deplete singly polyisoprenylated monomeric G-proteins in lung and breast cancer...
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EVpedia 2.0
DeCS - Términos Nuevos
DeCS - Términos Nuevos
DeCS - Términos Nuevos
Proteins11
- They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). (wikipedia.org)
- GTP hydrolysis is accelerated by GTPase activating proteins (GAPs), while GTP exchange is catalyzed by guanine nucleotide exchange factors (GEFs). (wikipedia.org)
- citation needed] The surrounding sequence helps determine the functional specificity of the small GTPase, for example the 'Insert Loop', common to the Rho subfamily, specifically contributes to binding to effector proteins such as IQGAP and WASP. (wikipedia.org)
- Scientists discovered before that GTP-hydrolases from the Rho/Rha family proteins are involved in the oncogenic events associated with ovarian cancer. (medicineinnovates.com)
- Rho/Rha activity is regulated by GTPase activating proteins (GAPs), guanine nucleotide dissociation inhibitors (GDIs) and guanine nucleotide exchange factors (GEFs). (medicineinnovates.com)
- The best characterized proteins within the group of GEFs are the Vav family proteins that play a major role in signal transduction and act as Rho/Rac protein modulators. (medicineinnovates.com)
- Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. (umbc.edu)
- As with other Rho family GTPases, the GDP/GTP cycling is regulated by GEFs (guanine nucleotide exchange factors), GAPs (GTPase-activating proteins) and GDIs (guanine nucleotide dissociation inhibitors). (umbc.edu)
- Polyisoprenylated cysteinyl amide inhibitors (PCAIs) are agents that mimic the essential posttranslational modifications of G-proteins. (oncotarget.com)
- Small G-proteins, monomeric GTPases, or the RAS (Rat sarcoma) superfamily are a large family of small guanine nucleotide-binding proteins with molecular weights ranging from 20 to 30 kDa [ 1 , 2 ]. (oncotarget.com)
- Accumulation of unfolded proteins in the ER lumen triggers the dissociation of GRP78 from its quiescent UPR mediators. (molvis.org)
GTPases5
- Guanosine nucleotide dissociation inhibitors (GDI) maintain small GTPases in the inactive state. (wikipedia.org)
- Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes. (cancerindex.org)
- We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca 2+ /calmodulin (Ca 2+ /CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor-mediated membrane recycling of Rab and Rho GTPases. (rupress.org)
- The class 1A phosphoinositide 3-kinase (PI3K) beta (PI3Kβ) is functionally unique in the ability to integrate signals derived from receptor tyrosine kinases (RTKs), heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs), and Rho-family GTPases. (elifesciences.org)
- Rho-family GTPases orchestrate both of these cellular processes. (silverchair.com)
GTPase3
- citation needed] Each subfamily shares the common core G domain, which provides essential GTPase and nucleotide exchange activity. (wikipedia.org)
- Rho GTPase activating protein 32 [Sour. (gsea-msigdb.org)
- p21-activated kinase 4 (PAK4), a specific effector of the Rho GTPase Cdc42, is activated by HGF, and we have previously shown that activated PAK4 induces a loss of both actin stress fibres and focal adhesions. (silverchair.com)
Subfamily1
- Cells were transfected with doxycycline-inducible vectors expressing either a pan-inhibitor of the R-Ras subfamily [dominant negative (DN) R-Ras] or enhanced green fluorescent protein (eGFP). (biomedcentral.com)
Exchange1
- Rho/Rac guanine nucleotide exchange fa. (gsea-msigdb.org)
Receptor1
- Furthermore, both robust phosphorylation of Homer3 and its dissociation from metabotropic glutamate receptor 1α (mGluR1α) were triggered by depolarization in primary cultured Purkinje cells, and these events were inhibited by CaMKII inhibitor. (jneurosci.org)
Overexpression1
- They also observed a significant overexpression of Vav3-alpha and Vav3.1 in the tumor specimens. (medicineinnovates.com)
Binds1
- The isolated PDZ domain (amino acids 206-334) is capable of folding into a well-behaved structure and binds to a nonpolar peptide with a dissociation constant (K(D)) of 1.9 microM, similar to that of the intact Tsp protein. (embl.de)
Family2
- citation needed] The Ras family is generally responsible for cell proliferation, Rho for cell morphology, Ran for nuclear transport and Rab and Arf for vesicle transport. (wikipedia.org)
- RHO family interacting cell polarizati. (gsea-msigdb.org)
Beta1
- PDZ domains consist of 80 to 90 amino acids comprising six beta-strands (beta-A to beta-F) and two alpha-helices, A and B, compactly arranged in a globular structure. (embl.de)
Source2
- adrenoceptor alpha 2B [Source:HGNC Sym. (gsea-msigdb.org)
- collagen type IV alpha 3 chain [Source. (gsea-msigdb.org)
Specific1
- Future research will aim at identifying specific inhibitors and/or inducers of UPR regulatory markers as well as expand the list of UPR-related animal models. (molvis.org)
Major2
- The major isoforms produced from the alternative splicing of Vav3 include full-length Vav3-alpha and N-terminal truncated Vav3.1 (which lack self-regulatory domains). (medicineinnovates.com)
- Rho2 activates the protein kinase C homolog Pck2, and Pck2 controls Mok1, the major (1-3) alpha-D-glucan synthase. (umbc.edu)
GTPASES8
- An abundantly-expressed rho GDP-dissociation inhibitor subtype that regulates a broad variety of RHO GTPASES . (nih.gov)
- Guanosine nucleotide dissociation inhibitors (GDI) maintain small GTPases in the inactive state. (wikipedia.org)
- The RHO family of small GTPases consists of at least 20 members which includes RHO, RAC, CDC42 and RND [ 3 ]. (biomedcentral.com)
- 6. The RHO Family GTPases: Mechanisms of Regulation and Signaling. (nih.gov)
- 7. Activation of type I phosphatidylinositol 4-phosphate 5-kinase isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42. (nih.gov)
- 11. Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases. (nih.gov)
- 13. DEF6, a novel PH-DH-like domain protein, is an upstream activator of the Rho GTPases Rac1, Cdc42, and RhoA. (nih.gov)
- 18. MLL regulates the actin cytoskeleton and cell migration by stabilising Rho GTPases via the expression of RhoGDI1. (nih.gov)
Guanosine2
- Guanosine 5'-triphosphate (GTP) binding protein alpha subunits (Galpha(i)) are known to participate in the regulation of force in airway smooth muscle. (asahq.org)
- 1 found that halothane and other volatile anesthetics at clinically relevant concentrations modulated the binding of guanine nucleotides to purified α subunits in aqueous solution, inhibiting the exchange of guanosine 5′-diphosphate (GDP) for a nonhydrolyzable analog of GTP (GTPγS). (asahq.org)
GEFs1
- RHOGTPases are highly regulated, they cycle between an active GTP-bound and an inactive GDP-bound state and this cycling is regulated by at least three distinct protein families: RHOGTPase guanine nucleotide exchange factors (GEFs), RHO activating proteins (GAPs) and RHO guanine nucleotide dissociation inhibitors (GDIs) [ 7 - 9 ]. (biomedcentral.com)
Kinase2
- Essential Role of Rho-Associated Kinase in ABO Immune Complex-Mediated Endothelial Barrier Disruption. (rochester.edu)
- Once formed, podocalyxin/ezrin complexes are very stable, because they are insensitive to actin depolymerization or inactivation of Rho kinase, which is known to be necessary for regulation of ezrin and to mediate Rho-dependent actin organization. (embl-heidelberg.de)
Inactivation1
- 20. Rho protein inactivation induced apoptosis of cultured human endothelial cells. (nih.gov)
Protein1
- The isolated PDZ domain (amino acids 206-334) is capable of folding into a well-behaved structure and binds to a nonpolar peptide with a dissociation constant (K(D)) of 1.9 microM, similar to that of the intact Tsp protein. (embl.de)
Branching enzyme1
- 1,4-alpha-glucan branching enzyme 1. (gsea-msigdb.org)
Source:HGNC Symbol1
- alpha fetoprotein [Source:HGNC Symbol. (gsea-msigdb.org)
Isoform1
- 9. Effects of lovastatin on Rho isoform expression, activity, and association with guanine nucleotide dissociation inhibitors. (nih.gov)
Amino Acids1
- PDZ domains consist of 80 to 90 amino acids comprising six beta-strands (beta-A to beta-F) and two alpha-helices, A and B, compactly arranged in a globular structure. (embl.de)
RHOA1
- The myosin inhibitor blebbistatin also stabilizes MTs, indicating that RhoA/ROCK act through myosin II to destabilize MTs. (exeter.ac.uk)
Inactive1
- then, we have how the cytosolic glycine breast of our projectorsparallel can begin well shown, conjugating the NOTCH1 cleavage of the inactive pathogen- enzymes into alpha. (evakoch.com)
Regulation1
- 17. Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. (nih.gov)
Cell2
- Key regulator of the integrin-mediated cell-matrix interaction signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. (nih.gov)
- The zebrafish embryo is an ideal model system for studying PGC migration due to 1) the transparency of the embryo, allowing in vivo analyses of cell migration and development, 2) the availability of various mutant stocks and the morpholino antisense oligo nucleotide gene knockdown system, and 3) the availability of PGC marker genes, for which localisation and functions are well characterised. (exeter.ac.uk)
Cells2
- 2. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, atorvastatin and simvastatin, induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation. (nih.gov)
- Microtubules regulate migratory polarity through Rho/ROCK signaling in T cells. (exeter.ac.uk)