Protein kinase C-dependent regulation of connexin43 gap junctions and hemichannels

2015 ◽  
Vol 43 (3) ◽  
pp. 519-523 ◽  
Author(s):  
Jette Skov Alstrom ◽  
Line Waring Stroemlund ◽  
Morten Schak Nielsen ◽  
Nanna MacAulay
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Gap Junctions ◽  
Fluorescent Dyes ◽  
Current Knowledge ◽  
Physiological Role ◽  
Kinase C ◽  
C Terminus ◽  
Gap Junctional ◽  
Connexin43 Gap Junctions

Connexin43 (Cx43) generates intercellular gap junction channels involved in, among others, cardiac and brain function. Gap junctions are formed by the docking of two hemichannels from neighbouring cells. Undocked Cx43 hemichannels can upon different stimuli open towards the extracellular matrix and allow transport of molecules such as fluorescent dyes and ATP. A range of phosphorylated amino acids have been detected in the C-terminus of Cx43 and their physiological role has been intensively studied both in the gap junctional form of Cx43 and in its hemichannel configuration. We present the current knowledge of protein kinase C (PKC)-dependent regulation of Cx43 and discuss the divergent results.

scholarly journals Identification of 14-3-3 proteins in human platelets: effects of synthetic peptides on protein kinase C activation

1996 ◽  
Vol 315 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Caroline P. D. WHEELER-JONES ◽  
Michele P. LEARMONTH ◽  
Harry MARTIN ◽  
Alastair AITKEN
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Synthetic Peptides ◽  
Physiological Role ◽  
Human Platelets ◽  
Kinase C ◽  
C Terminus ◽  
Protein Kinase C Activation

The 14-3-3 proteins inhibit protein kinase C (PKC) activity in vitro and contain conserved sequences that resemble the pseudosubstrate domain of PKC and the C-terminus of the annexins. In the present study we have identified the isoforms of 14-3-3 in human platelets and used synthetic peptides derived from the regions with similarity to PKC and annexins to examine the potential role of 14-3-3 in regulating platelet PKC activity. Immunoblotting studies with isoform-specific antisera raised against the acetylated peptides corresponding to the N-termini of 14-3-3 showed that these cells express high levels of the β, γ and ζ 14-3-3 isoforms. In addition, low levels of the ε and η 14-3-3 isoforms were detected. In washed, saponin-permeabilized platelets incubated with [γ-32P]ATP, thrombin- and phorbol 12-myristate 13-acetate (PMA)-induced phosphorylation of several proteins (66, 45, and 20 kDa) was inhibited by preincubation with AS peptide (KNVVGARRSSWRVISSIEQK) based on the pseudosubstrate-like region of the 14-3-3 family. A control peptide of similar size had no effect on PKC-mediated phosphorylation. PMA caused a rapid translocation of PKC activity from the cytosol to the particulate fraction of saponin-permeabilized platelets that was unaffected by either the AS peptide or a peptide derived from the annexin-like 14-3-3 domain (MKGDYYRYLAEVATGDD). These results suggest that isoforms of the 14-3-3 family may play an important physiological role as inhibitors of PKC activity in human platelets but are unlikely to be involved in controlling association of PKC with the membrane.

scholarly journals Physiological Role for Phosphatidic Acid in the Translocation of the Novel Protein Kinase C Apl II in Aplysia Neurons

2008 ◽  
Vol 28 (15) ◽  
pp. 4719-4733 ◽  
Author(s):  
Carole A. Farah ◽  
Ikue Nagakura ◽  
Daniel Weatherill ◽  
Xiaotang Fan ◽  
Wayne S. Sossin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidic Acid ◽  
Physiological Role ◽  
C2 Domain ◽  
The Novel ◽  
Physiological Conditions ◽  
Kinase C ◽  
Neuronal Membranes ◽  
Novel Protein

ABSTRACT In Aplysia californica, the serotonin-mediated translocation of protein kinase C (PKC) Apl II to neuronal membranes is important for synaptic plasticity. The orthologue of PKC Apl II, PKCε, has been reported to require phosphatidic acid (PA) in conjunction with diacylglycerol (DAG) for translocation. We find that PKC Apl II can be synergistically translocated to membranes by the combination of DAG and PA. We identify a mutation in the C1b domain (arginine 273 to histidine; PKC Apl II-R273H) that removes the effects of exogenous PA. In Aplysia neurons, the inhibition of endogenous PA production by 1-butanol inhibited the physiological translocation of PKC Apl II by serotonin in the cell body and at the synapse but not the translocation of PKC Apl II-R273H. The translocation of PKC Apl II-R273H in the absence of PA was explained by two additional effects of this mutation: (i) the mutation removed C2 domain-mediated inhibition, and (ii) the mutation decreased the concentration of DAG required for PKC Apl II translocation. We present a model in which, under physiological conditions, PA is important to activate the novel PKC Apl II both by synergizing with DAG and removing C2 domain-mediated inhibition.

scholarly journals Protein kinase C spatially and temporally regulates gap junctional communication during human wound repair via phosphorylation of connexin43 on serine368

2004 ◽  
Vol 167 (3) ◽  
pp. 555-562 ◽  
Author(s):  
Theresa S. Richards ◽  
Clarence A. Dunn ◽  
William G. Carter ◽  
Marcia L. Usui ◽  
John E. Olerud ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Wound Repair ◽  
Time Course ◽  
Phosphorylation Site ◽  
Primary Human Keratinocytes ◽  
Gap Junctional Communication ◽  
Kinase C ◽  
Junctional Communication ◽  
Gap Junctional

Phosphorylation of connexin43 (Cx43) on serine368 (S368) has been shown to decrease gap junctional communication via a reduction in unitary channel conductance. Examination of phosphoserine368 (pS368) in normal human skin tissue using a phosphorylation site–specific antibody showed relatively even distribution throughout the epidermal layers. However, 24 h after wounding, but not at 6 or 72 h, pS368 levels were dramatically increased in basal keratinocytes and essentially lost from suprabasal layers adjacent to the wound (i.e., within 200 μm of it). Scratch wounding of primary human keratinocytes caused a protein kinase C (PKC)-dependent increase in pS368 in cells adjacent to the scratch, with a time course similar to that found in the wounds. Keratinocytes at the edge of the scratch also transferred dye much less efficiently at 24 h, in a manner dependent on PKC. However, keratinocyte migration to fill the scratch required early (within <6 h) gap junctional communication. Our evidence indicates that PKC-dependent phosphorylation of Cx43 at S368 creates dynamic communication compartments that can temporally and spatially regulate wound healing.

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