Review
Connexin phosphorylation as a regulatory event linked to gap junction channel assembly

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Abstract

Gap junctions, composed of proteins from the connexin family, allow for intercellular communication between cells and are important in development and maintenance of cell homeostasis. Phosphorylation has been implicated in the regulation of gap junctional communication at several stages of the cell cycle and the connexin “lifecycle”, such as trafficking, assembly/disassembly, degradation, as well as in the gating of “hemi” channels or intact gap junction channels. This review focuses on how phosphorylation can regulate the early stages of the connexin life cycle through assembly of functional gap junctional channels. The availability of sequences from the human genome databases has indicated that the number of connexins in the gene family is approximately 20, but we know mostly about how connexin43 (Cx43) is regulated. Recent technologies and investigations of interacting proteins have shown that activation of several kinases including protein kinase A, protein kinase C (PKC), p34cdc2/cyclin B kinase, casein kinase 1 (CK1), mitogen-activated protein kinase (MAPK) and pp60src kinase can lead to phosphorylation of the majority of the 21 serine and two of the tyrosine residues in the C-terminal region of Cx43. While many studies have correlated changes in kinase activity with changes in gap junctional communication, further research is needed to directly link specific phosphorylation events with changes in connexin oligomerization and gap junction assembly.

Abbreviations

Cx
connexin
PKA
cAMP-dependent protein kinase
MAPK
mitogen-activated protein kinase
PKC
protein kinase C
CK1
casein kinase 1
PMA
phorbol 12-myristate 13-acetate
FSH
follicle stimulating hormone
NP
non-phosphorylated
SDS-PAGE
sodium dodecylsulfate-polyacrylamide gel electrophoresis

Keywords

Connexin
Gap junction
Phosphorylation
Cell signaling
PKC
PKA
Casein kinase

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