[Role of protein kinase C isozymes in cellular functions and pathological conditions].
Protein kinase C (PKC) is a superfamily of lipid-dependent protein Ser/Thr kinases consisting of at least 10 isozymes. The present article summarizes the papers presented at the congress symposium of the 74th Annual Meeting of the Japanese Pharmacological Society, in which six special topics regarding PKC isozyme-dependent cellular functions and pathological disorders were discussed. Using a GFP-tagged PKC expression technique, each PKC subtype was suggested to vary its targeting-site in each cell in response to each stimulus and that the targeting to the specific compartment is necessary for the specific cellular responses (NS). A cardioprotective agent, JTV519, was shown to attenuate post-ischemic myocardial injury by mimicking ischemic preconditioning through specific activation of PKC delta (YK). Using an antisense technique, PKC alpha and delta/epsilon were shown to be necessary for gene expression of inducible NO synthase by interleukin-1, one of the proinflammatory cytokines, by a stimulated transactivation of NF-kappa B (TH). In canine cerebral artery, PKC delta and PKC alpha play important roles in the development and the maintenance of vasospasm induced by subarachnoid hemorrhage, respectively (SN); and stretch-induced MLC20 phosphorylation involves MLCK and PKC alpha but not PKC delta activities facilitated by inactivation of myosin phosphatase through Rho activity (KO & KN). To clarify the role of PKC isozymes in insulin resistance, the effects of insulin on glucose uptake, PKC isozyme activation and PI3K activation in rat adipocytes were shown and then platelet PKC beta activation in diabetic patients with various diabetic complications, including diabetic retinopathy, was reported (TI). These studies will promisingly open the way to a new era for the development of novel drugs controlling an isozyme-specific activity of the protein kinase C superfamily and improvement in the knowledge about the role of the protein kinase in health and disease.
Hisayama
Tetsuhiro
T
Dept. of Pharmacology, Fac. of Pharmaceut. Sci, Univ. of Tokushima, Tokusima 770-8505, Japan. hisa@ph.tokushima-u.ac.jp
Nakayama
Koichi
K
Saito
Naoaki
N
Kihara
Yasuki
Y
Nishizawa
Shigeru
S
Obara
Kazuo
K
Ishizuka
Tatsuo
T
D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D007527:Isoenzymes; D018994:Myosin Light Chains; D011493:Protein Kinase C