Publication Date:
1998-02-07
Description:
The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nimnual, A S -- Yatsula, B A -- Bar-Sagi, D -- CA09176/CA/NCI NIH HHS/ -- CA28146/CA/NCI NIH HHS/ -- CA55360/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Jan 23;279(5350):560-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9438849" target="_blank"〉PubMed〈/a〉
Keywords:
Actins/metabolism
;
Animals
;
COS Cells
;
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
;
Cell Cycle Proteins/metabolism
;
Cell Line
;
Cell Membrane/ultrastructure
;
Enzyme Activation
;
GTP Phosphohydrolases/*metabolism
;
GTP-Binding Proteins/*metabolism
;
Guanine Nucleotide Exchange Factors
;
Guanosine Diphosphate/metabolism
;
Guanosine Triphosphate/metabolism
;
Humans
;
JNK Mitogen-Activated Protein Kinases
;
Membrane Proteins/chemistry/*metabolism
;
*Mitogen-Activated Protein Kinases
;
Proteins/metabolism
;
Proto-Oncogene Proteins
;
Recombinant Fusion Proteins/metabolism
;
Retroviridae Proteins, Oncogenic/chemistry
;
Signal Transduction
;
Son of Sevenless Proteins
;
Transfection
;
cdc42 GTP-Binding Protein
;
rac GTP-Binding Proteins
;
ras Guanine Nucleotide Exchange Factors
;
ras Proteins/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
