PHOSPHORYLATION SITES IN THE PDGF RECEPTOR WITH DIFFERENT SPECIFICITIES FOR BINDING GAP AND PI3 KINASE INVIVO
PHOSPHORYLATION SITES IN THE PDGF RECEPTOR WITH DIFFERENT SPECIFICITIES FOR BINDING GAP AND PI3 KINASE INVIVO
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DOI：
10.1002/j.1460-2075.1992.tb05182.x
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发表时间：
1992-04-01
期刊：
影响因子：
11.4
通讯作者：
COOPER, JA
中科院分区：
文献类型：
--
作者：
KASHISHIAN, A;KAZLAUSKAS, A;COOPER, JA
酪氨酸残基已在人血小板衍生生长因子（PDGF）受体β亚基中被鉴定，其磷酸化被PDGF刺激。这些位点也是体外自磷酸化位点。在激酶插入区域中总共有三个磷酸化位点，酪氨酸740、751和771。突变研究表明，Tyr740和751参与PDGF刺激的磷脂酰肌醇（PI）3激酶的结合，Tyr771是有效结合Ras的GTP酶激活剂GAP所必需的。仅在低PDGF受体水平下检测到对Tyr751的需求，表明其增加了PI3激酶结合的亲和力，但不是绝对必需的。激酶中的小缺失仅从Tyr740和Tyr771插入10个残基，并不显著降低PI3激酶或GAP的结合，表明远距离序列可能对识别不重要。这些数据表明，受体通过不同的磷酸化酪氨酸向不同的途径发出信号，并且某些蛋白质，如PI3激酶，可以识别单个受体中的两个磷酸化酪氨酸。
Tyrosine residues have been identified in the human platelet-derived growth factor (PDGF) receptor beta-subunit whose phosphorylation is stimulated by PDGF. These sites are also in vitro autophosphorylation sites. There are a total of three phosphorylation sites in the kinase insert region, tyrosines 740, 751 and 771. Mutagenesis studies show that Tyr740 and 751 are involved in the PDGF-stimulated binding of phosphatidylinositol (PI) 3 kinase, and Tyr771 is required for efficient binding of GAP, the GTPase activator of Ras. The requirement for Tyr751 is only detected at low PDGF receptor levels, suggesting that it increases the affinity of binding of PI3 kinase but is not absolutely required. Small deletions in the kinase insert only 10 residues from Tyr740 and Tyr771 do not significantly reduce binding of PI3 kinase or GAP, indicating that distant sequences are probably unimportant for recognition. The data suggest that the receptor signals to different pathways via different phosphorylated tyrosines, and that certain proteins, such as PI3 kinase, can recognize two phosphorylated tyrosines in a single receptor.