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Fig. 4. Pak functions in mammalian cells. Paks target the MAPK pathway by phosphorylating Raf1 at Ser338 and Mek1 at Ser298. These phosphorylations are necessary but not sufficient for MAPK activation. Paks also act upon a number of regulators of the cytoskeleton, including filamin, p41Arc, LIMK, merlin, myosin light chain kinase (MLCK) and stathmin. The net effect of these phosphorylations is to increase actin and tubulin polymerization. In addition, Paks phosphorylate steroid receptors such as the estrogen (ER) and progesterone (PR) receptors, which results in their activation, and the transcriptional co-repressor CtBP and the proapoptotic protein BAD, which results in their inactivation.





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