Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.

摘要: Abstract Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca 2 + -dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC family conventional α, β, and γ, novel -independent δ, ɛ, θ, η, atypical ξ, ι/λ isoforms. Inactive mainly cytosolic, upon activation it undergoes maturation, translocation the surface membrane, nucleus, endoplasmic reticulum, other cell organelles; process facilitated by scaffold proteins such as RACKs. Activated phosphorylates different substrates including ion channels, pumps, nuclear proteins. also CPI-17 leading inhibition MLC phosphatase, increased enhanced contraction. could initiate cascade kinases phosphorylation actin-binding calponin caldesmon, actin–myosin interaction, Increased activity has been associated with disorders ischemia–reperfusion injury, coronary artery disease, hypertension, diabetic vasculopathy. inhibitors test systems reduce hyperactivity disorders. First-generation staurosporine chelerythrine are not very specific. Isoform-specific ruboxistaurin have tested clinical trials. Target delivery pseudosubstrate inhibitory peptides siRNA may be useful localized disease. Further studies its should help design isoform-specific modulators that experimentally potent clinically safe target