Protein Kinase C- α and - ϵ Modulate Connexin-43 Phosphorylation in Human Heart

Bowling, Nancy; Huang, Xiaodi; Sandusky, George E.; Fouts, Rebecca L.; Mintze, Karen; Esterman, Michail A.; Allen, Paul D.; Maddi, Rosemarie; McCall, Eileen; Vlahos, Chris J.

doi:10.1006/jmcc.2000.1349

Cited by 72 publications

(47 citation statements)

References 21 publications

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“…Examination of the residues surrounding the S368 of Cx43 would, therefore, predict that this would be a PKCγ phosphorylation site while S262 would be a PKCε site. This has been found to be the case [56][57][58][59].…”

Section: Substrate Specificity Of Pkcε and Pkcγmentioning

confidence: 77%

“…In heart, functional Cx43 gap junctions are essential for conductance of electrical impulses and stabilization of synchrony. In attempts to identify which kinases phosphorylate Cx43, it was shown that both PKCα and PKCε phosphorylate Cx43 at multiple serines (S365, S368, S369, S372, and S373) in the C-terminus of Cx43 [56,57]. The antiarrhythmic peptide, Rotigaptide [97, see Fig.4], postponed dephosphorylation of Ser 297 and Ser 368 [58].…”

Section: If This Proves To Be the Case What Proteins Is Pkcε Bindingmentioning

confidence: 99%

See 1 more Smart Citation

Protein kinase C as a stress sensor

Barnett

Madgwick

Takemoto

2007

Cellular Signalling

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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.

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Section: Substrate Specificity Of Pkcε and Pkcγmentioning

confidence: 77%

Section: If This Proves To Be the Case What Proteins Is Pkcε Bindingmentioning

confidence: 99%

Protein kinase C as a stress sensor

Barnett

Madgwick

Takemoto

2007

Cellular Signalling

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show abstract

“…Conversely, phosphorylation of Ser-365 by protein kinase A (PKA) promotes gap junction assembly and communication (Burghardt et al, 1995;Solan et al, 2007;TenBroek et al, 2001). Although several isozymes of protein kinase C (PKC) phosphorylate connexin-43 in diverse cell types and tissues, PKC is the only isoform that phosphorylates it at the ID (Bowling et al, 2001;Doble et al, 2000;Lampe et al, 2000;Lin et al, 2003;Saez et al, 1997). Consistent with this, PKC suppresses gap junction communication in the ischemic heart through phosphorylation of connexin-43 at Ser-368 (Ek-Vitorin et al, 2006;Hund et al, 2007;Hund et al, 2008).…”

Section: Phosphorylation Regulates the Permeability Of Connexonsmentioning

confidence: 88%

Intercellular Connections in the Heart: The Intercalated Disc

Ackermann¹,

Hu²,

Kontrogianni‐Konstantopoulos³

2012

Cardiomyopathies - From Basic Research to Clinical Management

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“…The conductance and permeability of Hc, as well as gap junction channels, are regulated by intracellular protons changes (Ek-Vitorin et al, 1996;Morley et al, 1997;Spray & Burt, 1990) and calcium concentrations (Spray et al, 1985;Spray & Burt, 1990) but also via phosphorylation of specific serine, threonine and tyrosine residues by several kinases especially PKC (Bowling et al, 2001;Doble et al, 2000;. As indicated above, the conductance and permeability of the unapposed Cx43Hc are increased once Cx43 becomes dephosphorylated (Burt & Spray, 1988;Lau et al, 1991;Saez et al, 1986), while being reduced with increased Cx43 phosphorylation (Kwak & Jongsma, 1996).…”

Section: Unapposed Cx43hc Opening In Ischemia/reperfusion Injurymentioning

confidence: 90%

“…Cx43Hc, without affecting other key molecules in cellular function. Certainly, other isozymes have been demonstrated to phosphorylate Cx43, notably PKC (Bowling et al, 2001), but the functional implications in Cx43Hc regulation has not been assessed.…”

Section: Previous Findings and Implication For The Current Studymentioning

confidence: 99%