Connexin phosphorylation as a regulatory event linked to gap junction channel assembly.
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), p34(cdc2)/cyclin B kinase, casein kinase 1 (CK1), mitogen-activated protein kinase (MAPK) and pp60(src) 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.
Solan
Joell L
JL
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M5C800, Box 19024, Seattle, Washington 98109, United States.
Lampe
Paul D
PD
D000595:Amino Acid Sequence; D000818:Animals; D047389:Casein Kinase I / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002453:Cell Cycle; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism
D018031:Connexin 43; D017630:Connexins; D007473:Ion Channels; D000242:Cyclic AMP; D047389:Casein Kinase I; D011493:Protein Kinase C