Tyrosine phosphorylation of vav proto-oncogene product containing SH2 domain and transcription factor motifs.
Activation of receptor-linked and cytoplasmic protein tyrosine kinases is crucial in the control of normal and abnormal cell growth and differentiation. Some substrates of protein tyrosine kinases such as phospholipase C gamma and ras GTPase-activating protein (GAP) contain sequences homologous to the src protein domains SH2 and SH3 (refs 3-9). The proto-oncogene vav is expressed in haematopoietic cells and its product Vav contains sequence motifs commonly found in transcription factors, such as helix-loop-helix, leucine-zipper and zinc-finger motifs and nuclear localization signals, as well as a single SH2 and two SH3 domains. Here we show that stimulation of T-cell antigen receptor on normal human peripheral blood lymphocytes or on human leukaemic T cells, and the crosslinking of IgE receptors on rat basophilic leukaemia cells, both promote the phosphorylation of tyrosine residues in Vav. Moreover, activation of the receptor for epidermal growth factor leads to marked tyrosine phosphorylation of Vav in cells transiently expressing vav, and Vav associates with the receptor through its SH2 domain. We propose that vav encodes a new class of substrates whose tyrosine phosphorylation may provide a mechanism for direct signal transduction linking receptors at the cell surface to transcriptional control.
Margolis
B
B
Department of Pharmacology, New York University Medical Center, New York 10016.
Hu
P
P
Katzav
S
S
Li
W
W
Oliver
J M
JM
Ullrich
A
A
Weiss
A
A
Schlessinger
J
J
D016475:3T3 Cells; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D015153:Blotting, Western; D002461:Cell Line, Transformed; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D017455:Receptors, IgE; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; D014157:Transcription Factors; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; C496620:Vav1 protein, rat; D014443:Tyrosine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)