Protein kinase C as a stress sensor

Abstract

While there are many reviews which examine the group of proteins known as protein kinase C (PKC), the focus of this article is to examine the cellular roles of two PKCs that are important for stress responses in neurological tissues (PKCγ and ε) and in cardiac tissues (PKCε). These two kinases, in particular, seem to have overlapping functions and interact with an identical target, connexin 43 (Cx43), a gap junction protein which is central to proper control of signals in both tissues. While PKCγ and PKCε both help protect neural tissue from ischemia, PKCε is the primary PKC isoform responsible for responding to decreased oxygen, or ischemia, in the heart. Both do this through Cx43.It is clear that both PKCγ and PKCε are necessary for protection from ischemia. However, the importance of these kinases has been inferred from preconditioning experiments which demonstrate that brief periods of hypoxia protect neurological and cardiac tissues from future insults, and that this depends on the activation, translocation, or ability for PKCγ and/or PKCε to interact with distinct cellular targets, especially Cx43.This review summarizes the recent findings which define the roles of PKCγ and PKCε in cardiac and neurological functions and their relationships to ischemia/reperfusion injury. In addition, a biochemical comparison of PKC γ and PKC ε and a proposed argument for why both forms are present in neurological tissue while only PKC ε is present in heart, are discussed. Finally, the biochemistry of PKCs and future directions for the field are discussed, in light of this new information.

Protein kinase Cγ in colon cancer cells: Expression, Thr514 phosphorylation and sensitivity to butyrate-mediated upregulation as related to the degree of differentiation

“…This is followed by autophosphorylation of a position at the turn motif and another at the hydrophobic motif. With this, the maturation process is complete, the conventional PKC is primed and released as mature inactive PKC into the cytoplasm [14][15][16][17]. Upon activation, the primed PKC translocates to the plasma membrane.…”

“…Until recently, PKCγ was primarily associated with nerve tissue [32][33][34][35], and implicated in tissue injury repair [14,34]. Data on the expression of PKCγ in colon cancer cells or colon carcinomas are scarce.…”

“…It should be pointed out that the pan-antibody detects not only phosphorylation of PKCγ at Thr 514 but also other PKC isoenzymes phosphorylated at this or at a homologous position in the activation domain. Since these butyrate-induced effects are not seen with the antibody specific for pPKCγ-Thr 14 , it has to be considered that they are due to phosphorylation and dephosphorylation, respectively, of the activation domain in other PKC isoenzymes.…”

“…Although the exact mechanism and role of phosphorylation in PKC priming is not yet fully understood, it was suggested that a de novo synthesized conventional PKC first binds to a membrane, enabling a conformation that permits phosphoinositide-dependent protein kinase 1 (PDK-1) [12] to bind and phosphorylate a site in the activation-loop, which is Thr 514 for PKCγ [13,14]. Phosphorylation at this site leads to a conformational change enabling phosphorylations at two carboxyl-terminal sites namely, the turn motif and the hydrophobic motif, as a result of which the fully phosphorylated conventional PKC is released from the membrane, and positioned in its primed, inactive form in the cytoplasm [15][16][17].…”

Role of protein kinase C and mitochondrial permeability transition pore in the neuroprotective effect of ceramide in ischemia-induced cell death

“…PKC e is expressed in neural tissue, and it has been involved in protective roles against stroke and neural ischemia [10]. Besides, PKC e has been identified as a component of the mitoK ATP signalling cascade [11].…”