Publication Date:
1998-02-07
Description:
Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins. Vav, a guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3-kinase. The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, J -- Luby-Phelps, K -- Das, B -- Shu, X -- Xia, Y -- Mosteller, R D -- Krishna, U M -- Falck, J R -- White, M A -- Broek, D -- CA50261/CA/NCI NIH HHS/ -- CA71443/CA/NCI NIH HHS/ -- GM31278/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Jan 23;279(5350):558-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033-0800, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9438848" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Cell Line
;
Enzyme Activation
;
GTP Phosphohydrolases/*metabolism
;
GTP-Binding Proteins/*metabolism
;
Guanine Nucleotide Exchange Factors
;
Guanosine Diphosphate/*metabolism
;
Guanosine Triphosphate/metabolism
;
Inositol 1,4,5-Trisphosphate/metabolism/pharmacology
;
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism
;
Mutagenesis, Site-Directed
;
Oncogene Proteins/chemistry/*metabolism
;
Phosphatidylinositol 3-Kinases/*metabolism
;
Phosphatidylinositol 4,5-Diphosphate/metabolism/pharmacology
;
Phosphatidylinositol Phosphates/metabolism/pharmacology
;
Phosphatidylinositols/*metabolism/pharmacology
;
Phosphorylation
;
Proteins/metabolism
;
Proto-Oncogene Proteins c-vav
;
Rats
;
rac GTP-Binding Proteins
;
ras Guanine Nucleotide Exchange Factors
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
