PDGF BETA-RECEPTOR STIMULATES TYROSINE PHOSPHORYLATION OF GAP AND ASSOCIATION OF GAP WITH A SIGNALING COMPLEX
PDGF BETA-RECEPTOR STIMULATES TYROSINE PHOSPHORYLATION OF GAP AND ASSOCIATION OF GAP WITH A SIGNALING COMPLEX
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DOI：
10.1016/0092-8674(90)90220-9
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发表时间：
1990-04-06
期刊：
影响因子：
64.5
通讯作者：
WILLIAMS, LT
中科院分区：
文献类型：
--
作者：
KAPLAN, DR;MORRISON, DK;WILLIAMS, LT
血小板衍生生长因子（PDGF）刺激3 T3细胞和表达野生型PDGF受体的CHO细胞中的GT3活化蛋白（GAP）的酪氨酸磷酸化，但在表达有丝分裂信号缺陷的突变型受体的几个CHO细胞系中没有。在PDGF处理细胞后，GAP与PDGF受体和Raf-1，磷脂酶c-γ，和PI-3激酶，表明PDGF诱导信号分子复合物的形成。GAP与PDGF受体的关联和GAP的磷酸化在体外使用纯化的蛋白质和在表达鼠PDGF受体和人GAP的昆虫细胞中重建。然而，在由活化的c-Ha-ras转化的细胞中，其在对PDGF的某些反应中是缺陷的，GAP未能与PDGF受体结合或响应于PDGF而增加其磷酸酪氨酸含量。GAP与配体激活的PDGF受体的关联可能直接连接PDGF和ras信号通路。
Platelet-derived growth factor (PDGF) stimulated the tyrosine phosphorylation of the GTPase activating protein (GAP) in 3T3 cells and in CHO cells expressing wild-type PDGF receptors, but not in several CHO cell lines expressing mutant receptors defective in transmitting mitogenic signals. Following PDGF treatment of cells, GAP physically associated with the PDGF receptor and with Raf-1, phospholipase c-.gamma., and PI-3 kinase, suggesting that PDGF induced the formation of complexes of signaling molecules. The association of GAP with the PDGF receptor and the phosphorylation of GAP were reconstituted in vitro using purified protein and in insect cells expressing murine PDGF receptor and human GAP. However, in cells transformed by activated c-Ha-ras, which are defective in certain responses to PDGF, GAP failed to associate with the PDGF receptor or increase its phosphotyrosine content in response to PDGF. The association of GAP with ligand-activated PDGF receptors may directly link PDGF and ras signaling pathways.