Overview:

In mammals, there are several isoforms of p21-activated protein kinases or PAKs. PAKs 1, 2 and 3 are members of the serine/threonine p21-activating kinases that serve as targets for the small GTP binding proteins Cdc42 and RAC1. They have been implicated in wide range of biological activities, which include cytoskeletal reorganization, cellular proliferation and nuclear signaling. CDC42 and RAC1 induce autophosphorylation of PAK2, which stimulates sustained phosphorylation of other substrates (2). ERK phosphorylates and binds to Thr212 of PAK1. Thus, PAK1 may serve as a scaffold for a protein complex, which includes RAF, MEK and ERK (3).

References:

1. Martin, G A. et.al: A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20. EMBO J. 14: 1970-1978, 1995.

2. Jakobi R. et al: Substrates enhance autophosphorylation and activation of p21-activated protein kinase gamma-PAK in the absence of activation loop phosphorylation. Eur J Biochem 267:4414-4421, 2000.

3. Sundberg-Smith L J. et al: Adhesion stimulates PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. J Biol Chem. 2005 Jan 21;280(3):2055-64.