Find PAK1 Products Interaction Network for PAK1 PAK1 Details

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Synonyms: Alpha Pak, AW045634, MGC130000, MGC130001, Muk2, Pak, PAK1, PAK1B, PAKA, PAKALPHA

PAK Pathway

P21/Cdc42/Rac1-activated kinases (PAK) are down-stream effectors of the Rho-GTPases, Cdc42 and Rac-1. The PAC family of serine-threonine protein kinases includes two subfamily: Group I (PAK1, PAK2 and PAK3) and Group II (PAK4, PAK5 (7), and PAK6). PAK(s) along with other Cdc42 and Rac-1 down-stream effectors including WAVE, P15K, Formin, IQGAP and WASP regulate actin/myosin cytoskeleton structures to control a variety of cell processes. These processes include cell morphology, polarity, motility, division, macropinocytosis (cathrin-independent), and invasiveness.

PAKs are typically activated upon binding to GTP-bound Cdc42 or Rac-1 GTPases. Specificity of PAK activation by Cdc42 and Rac-1 resides, at least partially, in the co-localization of GEFs specific for each Rho-GTPase. PAK(s) facilitate p21-Ras-GTPase/Raf-1/Mek/ERK mitogenic signaling by directly phosphorylating Raf-1 and Mek1 which increases their associations with p21-Ras. PAK(s) are best known for their roles in the management of cell processes that involve actin/myosin cytoskeleton dynamic organization. PAK(s) phosphorylate LIM kinase (LIMK1) and myosin light chain kinase (MLCK). Phosphorylated LIM-kinase phosphorylates and inactivates cofilin, an actin depolymerase. This stabilizes actin filaments. Phosphorylated MLCK is unable to activate regulatory light chain myosin. RAK is reported to phosphorylate and inactivate the neurofibromatosis type 2 tumor suppressor (merlin). Merlin is reported to have a role in linking actin filaments to the plasma membrane.

There are many additional processes that are regulated by specific members of the PAK family. PAK-1 has been associated with the regulation of mitosis through phosphorylation of histone H3. PAK5 has been shown to localize to mitochondria and inhibit apoptosis by phosphorylating the Bcl-2 family member, BAD.