Figure 2

Signaling pathways of PAK1. The well-characterized upstream activators of PAK1 include the G protein-coupled receptors mediated Rho GTPases Cdc42 and Rac1, receptor tyrosine kinases mediated growth factor receptor-bound protein 2 (Grb2) and non-catalytic region of tyrosine kinase adaptor protein 1 (Nck), intergrins, serine/threonine kinases phosphatidylinositol 3 kinase (PI3K) and pyruvate dehydrogenase kinase isozyme 1 (PDK1) and Ras. A wide spectrum of substrates phosphorylated directly by PAK1 has been identified. Inhibition of of BAD, dynein light chain 1 (DLC1) and Merlin by PAK1 orchestrate to promote cancer cell survival. Likewise, activation of Raf1, forkhead in rhabdomyosarcoma (FKHR), MEK1, MEKK1 and estrogen receptor-α (ER-α) by PAK1 phosphorylation empower cancer cell to survive. PAK1 also phosphorylates substrates that regulate cytoskeletal dynamics, including myosin light-chain kinase (MLCK), LIM domain kinase (LIMK), p41-Arc and Merlin, cell motility is enhanced as a result.