It is now clear that loss of function of Ras GTPase-activating proteins (RasGAPs) is common in tumors, and germline mutations in certain RasGAP genes are responsible for some clinical syndromes. (nih.gov)
A mouse homologue of the Drosophila tumor suppressor l(2)tid gene defines a novel Ras GTPase-activating protein (RasGAP)-binding protein. (embl.de)
17. Regulation of extracellular signal-regulated kinase activity by p120 RasGAP does not involve its pleckstrin homology or calcium-dependent lipid binding domains but does require these domains to regulate cell proliferation. (nih.gov)
Tyrosine-phosphorylated3
In addition to its association with Ras, GAP has been shown to bind to several tyrosine-phosphorylated proteins in cells stimulated by growth factors or expressing transforming tyrosine kinase variants. (embl.de)
1. Changes in tyrosine-phosphorylated p190 and its association with p120 type I and p100 type II rasGAPs during myelomonocytic differentiation of human leukemic cells. (nih.gov)
3. Two SH2 domains of p120 Ras GTPase-activating protein bind synergistically to tyrosine phosphorylated p190 Rho GTPase-activating protein. (nih.gov)
SYNaptic3
SYNGAP1 is a gene that encodes the cytosolic protein SYNGAP1 ( SYNaptic GTPase Activating Protein ), an essential component of the postsynaptic density at excitatory glutamatergic neurons . (nih.gov)
The brain-specific synaptic guanosine triphosphatase (GTPase)-activating protein (SynGAP) is important in synaptic plasticity. (nih.gov)
Structural overview and comparative kinetic analysis of synaptic guanosine triphosphatase-activating proteins. (nih.gov)
SynGAP2
Here, we show that RapGAP activity of SynGAP requires its C2 domain. (nih.gov)
SynGAP presents the first example, to our knowledge, of a GAP that uses a second domain for catalytic activity, thus pointing to a new function of C2 domains. (nih.gov)
Tumor4
The RASSF family of tumor suppressors are essential to RAS-induced apoptosis and senescence, and constitute a barrier to RAS-mediated transformation. (nih.gov)
Here, we will examine how these effectors of RAS contribute to tumor suppression, through both RAS-dependent and RAS-independent mechanisms. (nih.gov)
Here we report the cloning and characterization of a novel GAP-binding protein, mTid-1, a DnaJ chaperone protein that represents the murine homolog of the Drosophila tumor suppressor l(2)tid gene. (embl.de)
7. The GTPase and Rho GAP domains of p190, a tumor suppressor protein that binds the M(r) 120,000 Ras GAP, independently function as anti-Ras tumor suppressors. (nih.gov)
P1207
Differential actions of p60c-Src and Lck kinases on the Ras regulators p120-GAP and GDP/GTP exchange factor CDC25Mm. (embl.de)
It is known that the human Ras GTPase activating protein (GAP) p120-GAP can be phosphorylated by different members of the Src kinase family and recently phosphorylation of the GDP/GTP exchange factor (GEF) CDC25Mm/GRF1 by proteins of the Src kinase family has been revealed in vivo [Kiyono, M., Kaziro, Y. & Satoh, T. (2000) J. Biol. (embl.de)
The phosphorylation of p120-GAP by p60c-Src inhibited its ability to stimulate the Ha-Ras-GTPase activity, whereas phosphorylation by Lck did not display any effect. (embl.de)
Our results suggest that phosphorylation by p60c-Src and Lck is a selective process that can modulate the activity of p120-GAP and CDC25Mm towards Ras proteins. (embl.de)
p120 GTPase-activating protein (GAP) down-regulates Ras by stimulating GTP hydrolysis of active Ras. (embl.de)
5. Aberrant Ras regulation and reduced p190 tyrosine phosphorylation in cells lacking p120-Gap. (nih.gov)
16. Role of p120 Ras-GAP in directed cell movement. (nih.gov)
Differentiation1
The Ras family of GTPases is a collection of molecular switches that link receptors on the plasma membrane to signaling pathways that regulate cell proliferation and differentiation. (embl.de)
Kinase2
KRAS binds tightly to RAF kinase in vitro , but activates RAF kinase only at the plasma membrane in vivo . (nih.gov)
10. A protein kinase C-independent pathway leading to c-Jun-dependent expression of 100-kDa Ras GTPase-activating protein in JEG-3 human choriocarcinoma cells. (nih.gov)
Effectors3
Pumping the brakes on RAS - negative regulators and death effectors of RAS. (nih.gov)
3. Further augmentation of the biochemical advances should be prioritized: one goal herein might be to develop an in vitro system in which RAS successfully functions in the plasma membrane to activate effectors. (nih.gov)
Project 1 aimed to determine which effectors are engaged by each of the mutant proteins, solve the structures of mutant RAS proteins complexed with relevant effectors, and identify new opportunities for small-molecule therapeutics. (nih.gov)
Tumors1
Mutants of Ras are found in 25-30% of human tumors. (embl.de)
Phosphorylation3
phosphorylation by Lck increased its capacity to stimulate the GDP/GTP exchange on Ha-Ras, whereas its phosphorylation by p60c-Src was ineffective. (embl.de)
8. Increased levels of p21ras-GTP and enhanced DNA synthesis accompany elevated tyrosyl phosphorylation of GAP-associated proteins, p190 and p62, in c-src overexpressors. (nih.gov)
15. Epidermal growth factor induces protein tyrosine phosphorylation and association of p190 with ras-GTP-ase activating protein in Caco-2 cells. (nih.gov)
Regulators2
However, aberrant upregulation of RAS activity often occurs in the absence of activating mutations in the RAS genes due to defects in RAS regulators. (nih.gov)
As it still remains unclear how these phosphorylations can influence the Ras pathway we have analyzed the ability of p60c-Src and Lck to phosphorylate these two Ras regulators and have compared the activity of the phosphorylated and unphosphorylated forms. (embl.de)
Intrinsic2
In contrast to the isolated GAP domain, which does not show any detectable RapGAP activity, a fragment comprising the C2 and GAP domains (C2-GAP) stimulates the intrinsic GTPase reaction of Rap by approximately 1 x 10(4). (nih.gov)
The accessory GTPase-activating proteins (GAPs) negatively regulate the cell signaling by increasing the slow intrinsic GTP to GDP hydrolysis rate of Ras. (embl.de)
Vitro1
12. rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. (nih.gov)
Characterization1
Progress in the characterization of processed full length KRAS4B and its interaction with cellular membranes stands as a highlight of the RAS Initiative to date. (nih.gov)
Distinct1
Our data support a catalytic mechanism similar to that of canonical RasGAPs and distinct from the canonical RapGAPs. (nih.gov)
Regulation1
Although regulation of RAS is central to their activity, RasGAPs exhibit great diversity in their binding partners and therefore affect signaling by multiple mechanisms that are independent of RAS. (nih.gov)
Involve1
1. The burgeoning industry collaborations that involve this RAS initiative should be used to identify lessons learned that guide development of a generalizable framework for how such activities might be extended going forward. (nih.gov)
Signal1
13. Targets of B lymphocyte antigen receptor signal transduction include the p21ras GTPase-activating protein (GAP) and two GAP-associated proteins. (nih.gov)
Expression1
Suppression of RASSF protein expression can also promote the development of excessive RAS signaling by uncoupling RAS from growth inhibitory pathways. (nih.gov)
Independent1
11. Complex formation between the p21ras GTPase-activating protein and phosphoproteins p62 and p190 is independent of p21ras signalling. (nih.gov)
Cells1
9. Protein tyrosine phosphatase PTP20 induces actin cytoskeleton reorganization by dephosphorylating p190 RhoGAP in rat ovarian granulosa cells stimulated with follicle-stimulating hormone. (nih.gov)
Role1
Despite its obvious importance for carcinogenesis, the role of Gln-61 in the GAP-stimulated GTPase activity of Ras has remained a mystery. (embl.de)
Small2
It shows dual specificity for the small guanine nucleotide-binding proteins Rap and Ras. (nih.gov)
All known oncogenic mutants of Ras map to a small subset of amino acids. (embl.de)
Development2
The screening approaches are leading the field into uncharted biological territory and appear wel positioned to serve as robust platforms for current and future collaborations and to accelerate the development of RAS-directed therapies. (nih.gov)
2. Continuing development of large-scale approaches to both identify and validate new compounds that selectively inhibit wild-type or mutant RAS. (nih.gov)