PAK Signaling in Oncogenesis

PAKs activated by extracellular signals participate in various signaling networks. PAK activate the mitogen-activated protein kinase (MAPK) pathway by phosphorylating Raf1 in addition to nuclear factor κB (NFκB). PAKs also phosphorylates a number of regulators of the cytoskeleton such as myosin light chain kinase (MLCK), LIM domain kinase (LIMK), filamin A, integrin linked kinase (ILK), merlin, Arpc1b, tubulin co-factor B (TCoB) and stathmin (OP18). In addition, PAKs regulate survival and apoptotic pathways through phosphorylation of its effectors such as dynein light chain 1 (DLC1), BimL and the pro-apoptotic protein BAD. On translocation to the nucleus, PAK directly affect gene transcription. Several transcription factors and transcriptional co-regulators such as FKHR, SHARP, C-terminal binding protein 1 (CTBP1) and Snail homologue 1 (SNAI1) are substrates to PAK1. PAK1 co-ordinates transcription, splicing and translation by phosphorylating Poly C-binding protein 1 (PCBP 1). PAKs also regulate cell cycle progression through phosphorylation of histone H3, Aurora A and polo like kinase 1(PlK1).

Publication

PAK Signaling in Oncogenesis. (2009) Poonam R. Molli, et al. Oncogene. 2009 Jul 16;28(28):2545-2555. Figure: F3. All organisms Homo sapiens Mus musculus Drosophila melanogaster

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