The protein kinase C family

Abstract

Protein kinase C represents a structurally homologous group of proteins similar in size, structure and mechanism of activation. They can modulate the biological function of proteins in a rapid and reversible manner. Protein kinase C participates in one of the major signal transduction systems triggered by the external stimulation of cells by various ligands including hormones, neurotransmitters and growth factors. Hydrolysis of membrane inositol phospholipids by phospholipase C or of phosphatidylcholine, generates sn-l,2-diacylglycerol, considered the physiological activator of this kinase. Other agents, such as arachidonic acid, participate in the activation of some of these proteins. Activation of protein kinase C by phorbol esters and related compounds is not physiological and may be responsible, at least in part, for their tumor-promoting activity. The cellular localization of the different calcium-activated protein kinases, their substrate and activator specificity are dissimilar and thus their role in signal transduction is unlike. A better understanding of the exact cellular function of the different protein kinase C isoenzymes requires the identification and characterization of their physiological substrates.The eukaryotic cell is a highly regulated entity, responding to its immediate intracellular environment as well as to external stimuli. Most regulations are mediated, either directly or indirectly, by conformational changes in proteins, and the equilibrium between active and inactive conformational states can be altered by both allosteric and covalent mechanisms. A most common covalent means of regulating protein activity is protein phosphorylation, which is particularly prominent for the role that it serves in signal transduction and is important in many other cellular responses (Edelman et al., 1987). Signals impinging on cells have their effects amplified and distributed by a network of protein phosphorylation and dephosphorylation reactions.

Protein kinase‐C mediates dual modulation of L‐type Ca2+ channels in human vascular smooth muscle

“…In comprise both fast and slow, long term components of this paper we demonstrate that TPA-induced activation action [12]. In cardiac muscle, 200 nM TPA was found of endogenous PKC modulates L-type Ca2' channels of human vascular smooth muscle cells in a dual manner.…”

Differential effects of fatty acid and phosholipid activators on the catalytic activities of a structurally novel protein kinase from rat liver

“…The regulatory properties of the enzyme are characterised by unusually high sensitivities to cardiolipin and C18 to C20 eisunsaturated fatty acids, as well as differential lipid specifities towards activation of its $6 peptide kinase and autophosphorylation activities. The lipid specificities, although overlapping, are distinct from the specificities observed for any of the PKCs particularly in relation to phosphatidylserine responsiveness [4,[6][7][8]. These properties and the unique structural features of its regulatory domain [26] suggest that liver PAK-1, together with the structurally similar protein kinases encoded by the recently described PKN cDNAs [3], are members of a new class of protein kinase within a super family of phospholipid-dependent protein kinases [1].…”

“…These properties and the unique structural features of its regulatory domain [26] suggest that liver PAK-1, together with the structurally similar protein kinases encoded by the recently described PKN cDNAs [3], are members of a new class of protein kinase within a super family of phospholipid-dependent protein kinases [1]. Of particular interest is the absence of the functional motifs characteristic of the PKC regulatory domains [3,26], including the zinc finger motifs implicated in diacylglycerol binding [4,[6][7][8] and the PKC pseudosubstrate motifs directly involved in the intramolecular inhibition of PKCs in the absence of phospholipid activators [17]. These structural differences can explain PAK-ls unresponsiveness to diacylglycerol and phorbol ester, as well as its basal $6 peptide kinase [1] and autophosphorylation (this paper) activities, which are characteristically high compared with the relatively very low basal activities of the PKCs [8][9][10][11].…”

“…The PKCs are structurally and functionally a diverse family of enzymes which includes the calcium-dependent (~, ill, fllI and Z) and independent (8, e, r/and 0) and the atypical (~', 2 and ft) isoenzymes [4][5][6][7][8][9][10]. All of the known PKCs are activated by phosphatidylserine, but not all are responsive to diacylglycerol or phorbol ester [5][6][7][8].…”

Expression of protein kinase C isozymes in hippocampal neurones in culture

“…Their role as mediators of signals generated upon external stimulation by hormones, neurotransmitters and growth factors has been widely and profusely documented (for recent reviews see [1][2][3]). In the brain, PKC's are highly concentrated and have been implicated in a broad spectrum of neuronal functions, such as modulation of ion channels [4], receptors [5] and neurotransmitter release [6].…”