Anderson D, Koch C A, Grey L, Ellis C, Moran M F, Pawson T
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Science. 1990 Nov 16;250(4983):979-82. doi: 10.1126/science.2173144.
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.
磷脂酶Cγ1（PLCγ1）和p21ras鸟苷三磷酸酶（GTPase）激活蛋白（GAP）可与活化的生长因子受体结合并被其磷酸化。PLCγ1和GAP均含有两个相邻的非催化性Src同源2（SH2）结构域拷贝。在细菌中单独合成的PLCγ1的SH2结构域可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共同表达时，可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PLCγ1的竞争。GAP SH2结构域与PDGF受体结合也获得了类似结果。其他信号蛋白（如p60src和Crk）的分离SH2结构域在体外也能结合活化的PDGF受体。因此，SH2结构域提供了一种共同机制，通过该机制，具有不同酶活性的调节蛋白可与相同的活化受体发生物理缔合，从而将生长因子刺激与细胞内信号转导途径偶联起来。
