Cell surface receptors activate p21-activated kinase 1 via multiple Ras and PI3-kinase-dependent pathways

摘要: Abstract p21-activated kinases (PAKs) were the first identified mammalian members of a growing family Ste20-like serine–threonine protein kinases. In this study, we show that PAK1 can be stimulated by carbachol, lysophosphatidic acid (LPA), epidermal growth factor (EGF), and phorbol 12-myristate 13-acetate (PMA) multiple independent overlapping pathways. Dominant-negative Ras, Rac, Cdc42 inhibited activation all these agonists, while active Rac1 sufficient to maximally activate in absence any treatment. Active Ras induced only weak could potentiated muscarinic receptor stimulation. Studies using inhibitors EGF tyrosine kinase, phosphatidylinositol 3-kinase (PI3-kinase) kinase C (PKC) revealed cell surface agonists through pathways PKC, PI3-kinase dependent pathway stimulate PAK1, stimulation was predominantly mediated EGF-R-dependent mechanism. Activation LPA receptor, but dominant-negative RhoA. These results identify Ras-dependent PAK1.