Phosphorylation-dependent activity-based conformational changes in P21-activated kinase family members and screening of novel ATP competitive inhibitors
Fig 10
Moleculer mechanistic insights into functional characteristics of PAK family.
PAKs are activated in response to extracellular stimuli and recruit diverse signaling pathways. PAKs are now known to be potential regulators of intracellular activity, cytoskeleton remodeling, cell survival, transformation, cell cycle and gene transcription pathways [57]. PAK2 activation by Rac, cdc42 cleavage, caspases or caspase-like proteases correlates with the programmed cell death. Thus, PAK2 is unique among the PAK isoforms due to its involvement in the stimulation of cell survival and cell death events depending on the activation mechanism [58]. Group II PAK signaling pathways have been observed downstream to membrane receptors and multiple potential regulators of intracellular activity. The three family members appear to have distinct and overlapping cellular functions and interact with an array of downstream effectors to elicit their cellular responses. EGF, epidermal growth factor; HGF, hepatocyte growth factor; PP1B, protein phosphatase 1B [21].