Margolis B, Hu P, Katzav S, Li W, Oliver J M, Ullrich A, Weiss A, Schlessinger J
Department of Pharmacology, New York University Medical Center, New York 10016.
Nature. 1992 Mar 5;356(6364):71-4. doi: 10.1038/356071a0.
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.
受体连接型和胞质蛋白酪氨酸激酶的激活在正常和异常细胞生长及分化的控制中至关重要。蛋白酪氨酸激酶的一些底物，如磷脂酶Cγ和ras GTP酶激活蛋白（GAP），含有与src蛋白结构域SH2和SH3同源的序列（参考文献3 - 9）。原癌基因vav在造血细胞中表达，其产物Vav含有转录因子中常见的序列基序，如螺旋-环-螺旋、亮氨酸拉链和锌指基序以及核定位信号，还有一个SH2结构域和两个SH3结构域。我们在此表明，刺激正常人外周血淋巴细胞或人白血病T细胞上的T细胞抗原受体，以及大鼠嗜碱性白血病细胞上IgE受体的交联，均能促进Vav中酪氨酸残基的磷酸化。此外，表皮生长因子受体的激活导致瞬时表达vav的细胞中Vav发生显著的酪氨酸磷酸化，并且Vav通过其SH2结构域与该受体结合。我们提出vav编码一类新的底物，其酪氨酸磷酸化可能提供一种将细胞表面受体与转录控制联系起来的直接信号转导机制。
