@entity16084 network in the regulation of phosphorylation and dephosphorylation of smooth muscle XXXX light chain.

@entity19077 @entity30265 @entity31050 @entity16084 @entity3999 @entity141
The contraction of smooth muscle is regulated primarily by intracellular @entity141 signal. It is well established that the elevation of the cytosolic @entity141 level activates @entity19077 , which phosphorylates 20 kDa regulatory @entity3999 light chain and activates @entity3999 ATPase. The simultaneous measurement of cytosolic @entity141 concentration and force development revealed that the alteration of the @entity141 -sensitivity of the contractile apparatus as well as the @entity141 signal plays a critical role in the regulation of smooth muscle contraction. The fluctuation of an extent of @entity3999 phosphorylation for a given change in @entity141 concentration is considered to contribute to the major mechanisms regulating the @entity141 -sensitivity. The level of @entity3999 phosphorylation is determined by the balance between phosphorylation and dephosphorylation. The phosphorylation level for a given @entity141 elevation is increased either by @entity141 -independent activation of phosphorylation process or inhibition of dephosphorylation. In the last decade, the isolation and cloning of @entity3999 phosphatase facilitated the understanding of regulatory mechanism of dephosphorylation process at the molecular level. The inhibition of @entity3999 phosphatase can be achieved by (1) alteration of hetrotrimeric structure, (2) phosphorylation of 110 kDa regulatory subunit @entity31050 at the specific site and (3) inhibitory protein @entity30265 upon its phosphorylation. Rho-kinase was first identified to phosphorylate @entity31050 , and later many kinases were found to phosphorylate @entity31050 and inhibit dephosphorylation of @entity3999 . Similarly, the phosphorylation of @entity30265 can be catalysed by multiple kinases. Moreover, the @entity3999 light chain can be phosphorylated by not only authentic @entity3999 light chain kinase in a @entity141 -dependent manner but also by multiple kinases in a @entity141 -independent manner, thus adding a novel mechanism to the regulation of the @entity141 -sensitivity by regulating the phosphorylation process. It is now clarified that the @entity16084 network is involved in the regulation of @entity3999 phosphorylation and dephosphorylation. However, the physiological role of each component remains to be determined. One approach to accomplish this purpose is to investigate the effects of the dominant negative mutants of the signalling molecule on the smooth muscle contraction. In this regards, a protein transduction technique utilizing the cell-penetrating peptides would provide a useful tool. In the preliminary study, we succeeded in introducing a fragment of @entity31050 into the arterial strips, and found enhancement of contraction.
