BINDING OF SH2 DOMAINS OF PHOSPHOLIPASE-C-GAMMA-1, GAP, AND SRC TO ACTIVATED GROWTH-FACTOR RECEPTORS
BINDING OF SH2 DOMAINS OF PHOSPHOLIPASE-C-GAMMA-1, GAP, AND SRC TO ACTIVATED GROWTH-FACTOR RECEPTORS
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DOI：
10.1126/science.2173144
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发表时间：
1990-11-16
期刊：
影响因子：
56.9
通讯作者：
PAWSON, T
中科院分区：
文献类型：
--
作者：
ANDERSON, D;KOCH, CA;PAWSON, T
磷脂酶C γ 1（PLC γ 1）和p21 ras鸟苷三磷酸酶（GTdR）激活蛋白（GAP）结合到激活的生长因子受体上并被其磷酸化。PLC γ 1和GAP都含有非催化Src同源2（SH 2）结构域的两个相邻拷贝。在细菌中单独合成的PLC γ 1的SH 2结构域与细胞裂解物中的表皮生长因子（EGF）-或血小板衍生生长因子（PDGF）-受体形成高亲和力复合物，并且当作为一种细菌蛋白一起表达时协同结合活化的受体。体外复合物的形成依赖于先前的生长因子刺激，并受到细胞内PLC γ 1的竞争。对于GAP SH 2结构域与PDGF受体的结合获得了类似的结果。其他信号蛋白如p60 src和Crk的分离的SH 2结构域也在体外结合活化的PDGF受体。因此，SH 2结构域提供了一种共同的机制，通过这种机制，酶促多样性调节蛋白可以与相同的活化受体物理结合，从而将生长因子刺激与细胞内信号转导途径偶联。
Phospholipase C.gamma.1 (PLC.gamma.1) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLC.gamma.1 and GAP contain two adjacent copies of the noncatalytic Src homology 2(SH2) domain. The SH2 domains of PLC.gamma.1 synthesized individually in bacteria formed high affinity complexes with the epidermal growth factor (EGF)- or platelet derived growth factor (PDGF)-receptors in cell lysates, and bound synergistically to activated receptors when expressed together as one bacterial protein. In vitro complex formation was dependent on prior growth factor stimulation and was competed by intracellular PLC.gamma.1. Similar results were obtained for binding of GAP SH2 domains to the PDGF-receptor. The isolated SH2 domains of other signaling proteins, such as p60src and Crk, also bound activated PDGF-receptors in vitro. SH2 domains, therefore, provide a common mechanism by which enzymatically diverse regulatory proteins can physically associate with the same activated receptors and thereby couple growth factor stimulation to intracellular signal transduction pathways.