Intracellular signal modulation: a pivotal role for protein kinase C.
1. Protein Kinase C represents a family of Ca(2+)- and phospholipid-dependent enzymes which catalyzes the covalent transfer of phosphate from ATP to serine and threonine residues on proteins. Phosphorylation of the substrate protein induces a conformational change and thereby a modification of its functional properties. 2. PKC family consists of at least twelve members, divided in three subgroups:classical PKCs, (alpha, beta I, beta II, gamma), new PKCs, (delta, epsilon, eta, theta, mu) and atypical PKCs, (zeta, lambda, iota). The three subgroups differ in cofactors requirements and tissue expression; these differences in co-activators dependency and regional distribution account for the differential activation profile of the various PKC isoenzymes. 3. Different molecules involved in the intracellular signaling network are phosphorylated "in vitro" and "in vivo" by PKC. Many target proteins show a preferential pattern of phosphorylation by the different PKC isotypes. 4. Through phosphorylation PKC modulates the functional activity of many different intracellular signaling systems which transport extracellular messages from the membrane to the nucleus. 5. The induction of apoptotic processes by the protein kinase inhibitor staurosporine indicates a possible role for PKC in the modulation of the intracellular mechanisms leading to Programmed Cell Death. 6. Abnormalities in both levels and activity of PKC, recently found in some chronic neurodegenerative syndromes, lead to the possibility that PKC dysfunction could be involved in the pathogenetic mechanisms of disease.
Casabona
G
G
I.N.M-Neuromed, Pozzilli, Italy.
D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009415:Nerve Net / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
D002352:Carrier Proteins; D007527:Isoenzymes; D011493:Protein Kinase C