Lck regulates Vav activation of members of the Rho family of GTPases.
Vav is a member of a family of oncogene proteins that share an approximately 250-amino-acid motif called a Dbl homology domain. Paradoxically, Dbl itself and other proteins containing a Dbl domain catalyze GTP-GDP exchange for Rho family proteins, whereas Vav has been reported to catalyze GTP-GDP exchange for Ras proteins. We present Saccharomyces cerevisiae genetic data, in vitro biochemical data, and animal cell biological data indicating that Vav is a guanine nucleotide exchange factor for Rho-related proteins, but in similar genetic and biochemical experiments we fail to find evidence that Vav is a guanine nucleotide exchange factor for Ras. Further, we present data indicating that the Lck kinase activates the guanine nucleotide exchange factor and transforming activity of Vav.
Han
J
J
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, School of Medicine, University of Southern California, Los Angeles 90033, USA.
Das
B
B
Wei
W
W
Van Aelst
L
L
Mosteller
R D
RD
Khosravi-Far
R
R
Westwick
J K
JK
Der
C J
CJ
Broek
D
D
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005347:Fibroblasts; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav; D011554:Pseudopodia; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000502:physiology*; D013489:Suppression, Genetic; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D018631:ras Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein; D019061:src-Family Kinases / Q000378:metabolism*
C073594:CDC24 protein, S cerevisiae; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; C057811:MCF2 protein, human; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C496618:VAV1 protein, human; C496620:Vav1 protein, rat; D006153:Guanosine Diphosphate; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein