Regulation of gap junctions by tyrosine protein kinases.
Most of the gap junction proteins are regulated in part by post-translational phosphorylation. Phosphorylation has been shown to be important in gap junction assembly and turnover, and for channel function in the resting state. Connexin phosphorylation may be altered by the activation of intracellular signaling pathways in response to growth factors, tumor promoters, activated oncogenes, hormones and inflammatory mediators. In some instances altered phosphorylation has been associated with changes in connexin function and in other cases appears to be associated with changes in the levels of the connexin protein and/or mRNA. This review focuses on the role of tyrosine protein kinases in the regulation of gap junctions. The literature is most extensive for connexin43 and those studies are reviewed here. A great deal has been learned in recent years about how connexin43 is regulated by tyrosine kinase-dependent signaling pathways. These pathways are often complex and to some extent are cell type- and stimulus-dependent. Although considerable progress has been made in unraveling the cellular pathways that regulate connexin function, significant challenges remain to be addressed in identifying additional phosphorylation sites and determining the stoichiometries of the phosphorylation events that regulate connexin function and it's interaction with other cellular proteins.
Warn-Cramer
Bonnie J
BJ
Natural Products Program, Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Lau
Alan F
AF
D000818:Animals; D018031:Connexin 43 / Q000737:chemistry / Q000502:physiology; D017630:Connexins / Q000378:metabolism / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
D018031:Connexin 43; D017630:Connexins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases