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- _6 value " The relative contributions of the EC MLCK and Rho pathways in regulating EC permeability are not well understood: inhibition of either MLCK activity (50) or Rho activation (16, 18) attenuates thrombin-induced EC barrier dysfunction. A recent report suggests that Rho/Rho kinase and MLCK may differentially regulate MLC phosphorylation according to spatial localization within cultured cells (144). Additional complexity in the system is provided by the contribution of the p21-activated kinase (PAK) family, downstream effectors of the small GTPases Rac and Cdc42. Isoforms PAK1 and PAK2 have both been shown to phosphorylate smooth muscle MLCK and decrease MLCK activity in cultured cells (61, 123), but whether PAK regulates the high-molecular-mass MLCK present in endothelium in this fashion is not clear. Conversely, PAK2 can directly phosphorylate MLC to produce EC contraction (163)." provenance.
- _6 wasQuotedFrom 11568129 provenance.