Manser E, Loo T H, Koh C G, Zhao Z S, Chen X Q, Tan L, Tan I, Leung T, Lim L
Glaxo-IMCB Group, Institute of Molecular and Cell Biology, Singapore.
Mol Cell. 1998 Jan;1(2):183-92. doi: 10.1016/s1097-2765(00)80019-2.
The PAK family of kinases are regulated through interaction with the small GTPases Cdc42 and Rac1, but little is known of the signaling components immediately upstream or downstream of these proteins. We have purified and cloned a new class of Rho-p21 guanine nucleotide exchange factor binding tightly through its N-terminal SH3 domain to a conserved proline-rich PAK sequence with a Kd of 24 nM. This PAK-interacting exchange factor (PIX), which is widely expressed and enriched in Cdc42- and Rac1-driven focal complexes, is required for PAK recruitment to these sites. PIX can induce membrane ruffling, with an associated activation of Rac1. Our results suggest a role for PIX in Cdc42-to-Rac1 signaling, involving the PIX/PAK complex.
丝氨酸/苏氨酸蛋白激酶PAK家族通过与小GTP酶Cdc42和Rac1相互作用来调节，但对这些蛋白上下游直接的信号传导成分了解甚少。我们已经纯化并克隆了一类新的Rho-p21鸟嘌呤核苷酸交换因子，它通过其N端SH3结构域与保守的富含脯氨酸的PAK序列紧密结合，解离常数为24 nM。这种与PAK相互作用的交换因子（PIX）广泛表达，并在由Cdc42和Rac1驱动的粘着斑复合体中富集，它是PAK募集到这些位点所必需的。PIX可以诱导膜皱襞形成，并伴有Rac1的激活。我们的结果表明PIX在Cdc42到Rac1的信号传导中发挥作用，涉及PIX/PAK复合体。
