Temporal regulation of connexin phosphorylation in embryonic and adult tissues.
Gap junctions, composed of proteins from the connexin family, allow for intercellular communication between cells in tissues and are important in development, tissue/cellular homeostasis, and carcinogenesis. Genome databases indicate that there are at least 20 connexins in the mouse and human. Connexin phosphorylation has been implicated in connexin assembly into gap junctions, gap junction turnover, and cell signaling events that occur in response to tumor promoters and oncogenes. Connexin43 (Cx43), the most widely expressed and abundant gap junction protein, can be phosphorylated at several different serine and tyrosine residues. Here, we focus on the dynamic regulation of Cx43 phosphorylation in tissue and how these regulatory events are affected during development, wound healing, and carcinogenesis. The activation of several kinases, including protein kinase A, protein kinase C, p34cdc2/cyclin B kinase, casein kinase 1, mitogen-activated protein kinase, and pp60src kinase, can lead to the phosphorylation of different residues in the C-terminal region of Cx43. The use of antibodies specific for phosphorylation at defined residues has allowed the examination of specific phosphorylation events both in tissue culture and in vivo. These new antibody tools and those under development will allow us to correlate specific phosphorylation events with changes in connexin function.
King
Timothy J
TJ
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M5C800, Box 19024, Seattle, WA 98109, USA.
Lampe
Paul D
PD
D000818:Animals; D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism / Q000502:physiology*; D017630:Connexins / Q000235:genetics* / Q000378:metabolism*; D030541:Databases, Genetic; D005123:Eye / Q000196:embryology / Q000378:metabolism; D017629:Gap Junctions; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006321:Heart / Q000196:embryology; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D012867:Skin / Q000196:embryology / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing
D018031:Connexin 43; D017630:Connexins