Members of the protein kinase C (PKC) family of serine/threonine kinases play
critical roles in the regulation of cellular differentiation and proliferation of diverse
cell types. Protein kinase C (PKC) is the major phorbol ester receptor. Nine
mammalian members of the PKC family have been identified and designated alpha,
beta, gamma, delta, epsilon, zeta, eta, theta, and lambda.
NCBI Summary:
Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a constitutive kinase activity which is independent of calcium, and PKC activators, phosphatidylserine and diacylglycerol. Furthermore, it is insensitive to PKC inhibitors and cannot be activated by phorbol ester. The structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC.
General function
Intracellular signaling cascade
Comment
Cellular localization
Secreted
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Ovarian function
Follicle development, Early embryo development
Comment
Oocyte activation, phospholipase C zeta and human infertility. Kashir J et al. BACKGROUND Mammalian oocytes are activated by intracellular calcium (Ca(2+)) oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C zeta, PLCzeta, which is introduced into the oocyte following membrane fusion, as the responsible factor. This review summarizes the current understanding of human oocyte activation failure and describes recent discoveries linking certain cases of male infertility with defects in PLCzeta expression and activity. How these latest findings may influence future diagnosis and treatment options are also discussed. METHODS Systematic literature searches were performed using PubMed, ISI-Web of Knowledge and The Cochrane Library. We also scrutinized material from the United Nations and World Health Organization databases (UNWHO) and the Human Fertilization and Embryology Authority (HFEA). RESULTS AND CONCLUSIONS Although ICSI results in average fertilization rates of 70%, complete or virtually complete fertilization failure still occurs in 1-5% of ICSI cycles. While oocyte activation failure can, in some cases, be overcome by artificial oocyte activators such as calcium ionophores, a more physiological oocyte activation agent might release Ca(2+) within the oocyte in a more efficient and controlled manner. As PLCzeta is now widely considered to be the physiological agent responsible for activating mammalian oocytes, it represents both a novel diagnostic biomarker of oocyte activation capability and a possible mode of treatment for certain types of male infertility.
Expression regulated by
LH
Comment
Activation of protein kinase Czeta mediates luteinizing hormone- or forskolin-induced NGFI-B expression in preovulatory granulosa cells of rat ovary. Park JI et al. We have previously demonstrated that luteinizing hormone (LH) induces a rapid and transient expression of NGFI-B in the ovary. In this report, we investigated the signaling pathway for LH- and forskolin-induced NGFI-B expression in cultured rat granulosa cells of preovulatory follicles. LH- or forskolin-induced NGFI-B expression was suppressed by high dose of protein kinase C (PKC) inhibitor RO 31-8220 (10muM), but not by low doses RO 31-8220 (0.1-1.0muM) or adenylate cyclase inhibitor MDL-12,300A, implicating the involvement of atypical PKCs. Kinase assay revealed that LH treatment of granulosa cells resulted in a rapid stimulation of atypical PKCzeta activity. Interestingly, like LH, forskolin was also able to activate PKCzeta. Treatment with the cell-permeable PKCzeta-specific inhibitor pseudosubstrate peptide inhibited LH-or forskolin-induced NGFI-B expression, indicating the essential role of PKCzeta. Consistent with this promise, in granulosa cells depleted of diacylglycerol sensitive PKCs by prolonged treatment with tetradecanoylphobol-13-acetate, LH or forskolin could still induce NGFI-B expression, and RO 31-8220 or the PKCzeta pseudosubstrate peptide inhibited LH- or forskolin-induced NGFI-B expression. Furthermore, overexpression of dominant-negative PKCzeta in primary granulosa cells using a replication-defective adenovirus vector resulted in the suppression of LH- or forskolin-induced NGFI-B expression. Our findings demonstrate that PKCzeta, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles.
Ovarian localization
Oocyte, Granulosa
Comment
Peluso JJ, et al reported that basic fibroblast growth factor maintains calcium homeostasis
and granulosa cell viability by stimulating calcium efflux via
a PKC delta-dependent pathway.
Previous studies have demonstrated that basic fibroblast growth factor
prevents granulosa cell apoptosis. Granulosa cells, as well as spontaneously immortalized
granulosa cells, were shown to express PKC delta, -lambda, and -zeta. Finally,
the PKC delta -specific inhibitor, rottlerin, blocked basic fibroblast growth
factor's antiapoptotic action in granulosa cells and spontaneously
immortalized granulosa cells. These studies suggest that basic fibroblast
growth factor regulates intracellular free calcium through a PKC delta
-dependent mechanism and that a sustained increase in intracellular free
calcium is sufficient to induce and is required for granulosa cell apoptosis.