Fantl W J, Escobedo J A, Martin G A, Turck C W, del Rosario M, McCormick F, Williams L T
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Cell. 1992 May 1;69(3):413-23. doi: 10.1016/0092-8674(92)90444-h.
The receptor for platelet-derived growth factor (PDGF) binds two proteins containing SH2 domains, GTPase activating protein (GAP) and phosphatidylinositol 3-kinase (PI3-kinase). The sites on the receptor that mediate this interaction were identified by using phosphotyrosine-containing peptides representing receptor sequences to block specifically binding of either PI3-kinase or GAP. These results suggested that PI3-kinase binds two phosphotyrosine residues, each located in a 5 aa motif with an essential methionine at the fourth position C-terminal to the tyrosine. Point mutations at these sites caused a selective elimination of PI3-kinase binding and loss of PDGF-stimulated DNA synthesis. Mutation of the binding site for GAP prevented the receptor from associating with or phosphorylating GAP, but had no effect on PI3-kinase binding and little effect on DNA synthesis. Therefore, GAP and PI3-kinase interact with the receptor by binding to different phosphotyrosine-containing sequence motifs.
血小板衍生生长因子（PDGF）受体可结合两种含有SH2结构域的蛋白，即GTP酶激活蛋白（GAP）和磷脂酰肌醇3激酶（PI3激酶）。通过使用代表受体序列的含磷酸酪氨酸肽来特异性阻断PI3激酶或GAP的结合，从而确定了受体上介导这种相互作用的位点。这些结果表明，PI3激酶结合两个磷酸酪氨酸残基，每个残基位于一个5个氨基酸的基序中，在酪氨酸C末端的第四个位置有一个必需的甲硫氨酸。这些位点的点突变导致PI3激酶结合的选择性消除以及PDGF刺激的DNA合成丧失。GAP结合位点的突变阻止了受体与GAP结合或使其磷酸化，但对PI3激酶结合没有影响，对DNA合成影响很小。因此，GAP和PI3激酶通过结合不同的含磷酸酪氨酸序列基序与受体相互作用。
