c-Src: bridging the gap between phosphorylation- and acidification-induced gap junction channel closure.
Gap junctions are a unique type of intercellular junction that mediate the direct exchange of small molecules between neighboring cells and play critical roles in the normal function of numerous organs. Mutations in the connexin proteins that make up gap junctions have been implicated in numerous human skin and neurosensory disorders. The ability of gap junctions to transmit molecules between cells is regulated by intracellular pH, the phosphorylation state of connexin, and the interaction of connexin with other cellular proteins. This Perspective focuses on the novel and complex events initiated by intracellular acidification resulting from tissue ischemia or hypoxia that lead to the interruption of intercellular communication between astrocytes. These events include alterations in connexin43 (Cx43) phosphorylation, disruption of beta-actin binding to Cx43, and the induced interaction of Cx43 with the c-Src tyrosine kinase, extracellular signal-regulated kinase 1 and 2, and mitogen-activated protein kinase phosphatase 1.
Natural Products and Cancer Biology Program, Cancer Research Center, University of Hawaii at Manoa, Honolulu, HI 96813, USA. aflau@crch.hawaii.edu
Alan F
AF
Lau
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002450:Cell Communication / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D018031:Connexin 43 / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1; D017629:Gap Junctions / Q000502:physiology*; D016391:Genes, src; D006863:Hydrogen-Ion Concentration; D017874:Immediate-Early Proteins / Q000378:metabolism; D007424:Intracellular Fluid / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D025941:Protein Interaction Mapping; D054645:Protein Phosphatase 1; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*
D018797:Cell Cycle Proteins; D018031:Connexin 43; D017874:Immediate-Early Proteins; D010768:Phosphoserine; D016392:Proto-Oncogene Proteins pp60(c-src); D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases