title: p21-activated kinase 1 (PAK1) can promote ERK activation in a kinase-independent manner.
abstract: PAK1 plays an important role in proliferation and tumorigenesis, at least partially by promoting ERK phosphorylation of C-RAF (Ser-338) or MEK1 (Ser-298). We observed how that overexpression of a kinase-dead mutant form of PAK1 increased phosphorylation of MEK1/2 (Ser-217/Ser-221) and ERK (Thr-202/Tyr-204), although phosphorylation of B-RAF (Ser-445) and C-RAF (Ser-338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1, and MEK1 independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulate MEK activity in a kinase-independent manner, probably by serving as a scaffold to facilitate interaction of C-RAF.
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors: Zhipeng
authors: Z
authors: Wang
authors: Meng
authors: M
authors: Fu
authors: Lifeng
authors: L
authors: Wang
authors: Juanjuan
authors: J
authors: Liu
authors: Yuhua
authors: Y
authors: Li
authors: Cord
authors: C
authors: Brakebusch
authors: Qibing
authors: Q
authors: Mei
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D009479:Neuropeptides; C107953:RAC1 protein, human; C484602:Rac1 protein, mouse; C482128:MAP2K2 protein, human; C482119:BRAF protein, human; C482120:Braf protein, mouse; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D054462:p21-Activated Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; C482127:Map2k1 protein, mouse; C482129:Map2k2 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein
keywords: ERK; MAP Kinases (MAPKs); MEK; PAK; RAF; Rac1; Scaffold Proteins
references: Annu Rev Biochem. 2003;72:743-81
references: 12676796
references: Nature. 1998 Nov 12;396(6707):180-3
references: 9823899
references: Cancer Metastasis Rev. 2009 Jun;28(1-2):51-63
references: 19165420
references: EMBO J. 1991 Apr;10(4):885-92
references: 1849075
references: Clin Cancer Res. 2012 Jul 15;18(14):3743-9
references: 22595609
references: J Cell Biol. 2009 May 4;185(3):409-22
references: 19414607
references: Nat Cell Biol. 2008 Nov;10(11):1356-64
references: 18931661
references: Oncogene. 2010 Jun 10;29(23):3362-73
references: 20383193
references: Biochim Biophys Acta. 2010 Sep;1803(9):1106-13
references: 20595063
references: J Cell Biol. 2003 Jul 21;162(2):281-91
references: 12876277
references: J Biol Chem. 2005 Nov 4;280(44):36609-15
references: 16129686
references: J Biol Chem. 1996 Oct 18;271(42):25746-9
references: 8824201