Chardin P, Cussac D, Maignan S, Ducruix A
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS 660, Valbonne, France.
FEBS Lett. 1995 Aug 1;369(1):47-51. doi: 10.1016/0014-5793(95)00578-w.
Grb2 is an 'adaptor' protein made of one SH2 and two SH3 domains. The SH3 domains bind to prolinerich motifs in the C-terminal part of the ras exchange factor Sos. Binding of the Grb2 SH2 domain to phosphotyrosine motifs on receptors, or other adaptor proteins such as Shc, recruits this Grb2/Sos complex at the plasma membrane where Sos stimulates nucleotide exchange on ras, then ras activates raf and leads to MAP kinase activation. The structure of Grb2, the precise motifs recognised by its SH2 and SH3 domains, the way Grb2 performs its function, a possible regulation of its association with Sos, and its ability to complex with other proteins in vivo, are discussed.
Grb2是一种由一个SH2结构域和两个SH3结构域组成的“衔接子”蛋白。SH3结构域与ras交换因子Sos C末端富含脯氨酸的基序结合。Grb2的SH2结构域与受体上的磷酸酪氨酸基序或其他衔接子蛋白（如Shc）结合，可将这种Grb2/Sos复合物募集到质膜上，在那里Sos刺激ras上的核苷酸交换，然后ras激活raf并导致丝裂原活化蛋白激酶（MAP激酶）激活。本文讨论了Grb2的结构、其SH2和SH3结构域识别的精确基序、Grb2发挥功能的方式、其与Sos结合的可能调控以及它在体内与其他蛋白质形成复合物的能力。
