Phorbol Myristate Acetate-Induced Changes in Protein Kinase C Isozymes (α, β, γ and ζ) in Human T Cell Subsets
Part of the
Advances in Experimental Medicine and Biology
book series (AEMB, volume 365)
Protein kinase C (PKC), a serine/threonine kinase, plays an important role in downstream signaling pathway of T cell activation (1,2). Activation of PKC produces varied, and at times disparate, cell specific responses. In T cells, direct activation of PKC results in an induction of interleukin-2 receptor (IL-2R) expression and IL-2 production, initiation of DNA synthesis, and regulation of cytotoxic function (3–11). Although PKC was originally thought to be a single molecule, recent molecular and biochemical studies have revealed that PKC exists as a family of different isozymes that differ in their structure, dependence on Ca++, tissue distribution and substrate specificity (12–15). They have been broadly categorized into three major subgroups; Group 1 including classical Ca++-dependent PKCs (α, β and γ); Group 2 comprised of Ca++-independent PKCs (δ, ϵ, η, θ); and Group 3, consisting of atypical PKC (ζ, λ). PKCζ isozyme is considered to be resistant to the effect of phorbol esters (12). Ways et al (16), using a variety of non-lymphoid cell lines, have failed to demonstrate translocation of PKCζ following stimulation with phorbol ester. To the best of our knowledge there is no study of PKCζ in normal human peripheral blood T cells. Further there is a controversy regarding the role of PKCβ isozyme T cell functions (17–19) and regarding the presence of PKCγ in T cells (22–26). In this study we examined the translocation of Ca++-dependent (PKCα, β, γ) and atypical (PKCζ) PKC isozymes in human peripheral blood T cells. This study demonstrates that PKC isozymes are differentially translocated among CD4+ and CD8+ T cells and PKCγ isozyme is present in T cells and translocated following PMA activation.
KeywordsPhorbol Myristate Acetate Phorbol Ester Phorbol Myristate Acetate Normal Human Peripheral Blood Cell Specific Response
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