• 4. RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion. (nih.gov)
  • 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)
  • 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)
  • 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)
  • 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)
  • A mouse homologue of the Drosophila tumor suppressor l(2)tid gene defines a novel Ras GTPase-activating protein (RasGAP)-binding protein. (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)
  • 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)
  • 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)
  • KRAS binds tightly to RAF kinase in vitro , but activates RAF kinase only at the plasma membrane in vivo . (nih.gov)
  • 12. rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. (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)
  • 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)
  • 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)
  • 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)
  • 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)
  • The RAS Initiative, under the expert direction of Dr. Frank McCormick, has achieved considerable success in each of its projects. (nih.gov)
  • 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)
  • The FNLAC RAS Working Group was formed to advise various strategic, technical, and scientific aspects of the NCI RAS Initiative, and to present its findings and recommendations to the Frederick National Laboratory Advisory Committee (FNLAC). (nih.gov)
  • Specific goals included: (1) provision of feedback and suggestions to Dr. Frank McCormick and his team at FNLCR, (2) regular, candid assessments of program aspects that are working wel and areas where improvements or pivots might be needed, and (3) ensuring optimal connectivity between the FNLCR RAS initiative and the extramural community. (nih.gov)
  • When the RAS Initiative was established, Dr. McCormick articulated five projects that would be pursued during the initial 5-year funding period. (nih.gov)
  • Thereafter, RAS Initiative efforts were consolidated around the remaining four projects based on their increasing momentum as wel as decisions regarding the optimal alignment of domain expertise resident at FNLCR. (nih.gov)
  • Our data support a catalytic mechanism similar to that of canonical RasGAPs and distinct from the canonical RapGAPs. (nih.gov)
  • Mutants of Ras are found in 25-30% of human tumors. (embl.de)
  • 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)
  • 13. Targets of B lymphocyte antigen receptor signal transduction include the p21ras GTPase-activating protein (GAP) and two GAP-associated proteins. (nih.gov)
  • Thus, it is important to understand the mechanics of RAS-membrane interaction not only to clarify RAS signal transduction, but also to facilitate future drug discovery efforts directed against RAS itself. (nih.gov)
  • 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)
  • The brain-specific synaptic guanosine triphosphatase (GTPase)-activating protein (SynGAP) is important in synaptic plasticity. (nih.gov)
  • It shows dual specificity for the small guanine nucleotide-binding proteins Rap and Ras. (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)
  • All known oncogenic mutants of Ras map to a small subset of amino acids. (embl.de)