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FEBS Lett. 2014 Apr 17;588(8):1423-9. doi: 10.1016/j.febslet.2014.01.049. Epub 2014 Feb 4.

Specific Cx43 phosphorylation events regulate gap junction turnover in vivo.

Author information

1
Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States.
2
Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States. Electronic address: plampe@fhcrc.org.

Abstract

Gap junctions, composed of proteins from the connexin gene family, are highly dynamic structures that are regulated by kinase-mediated signaling pathways and interactions with other proteins. Phosphorylation of Connexin43 (Cx43) at different sites controls gap junction assembly, gap junction size and gap junction turnover. Here we present a model describing how Akt, mitogen activated protein kinase (MAPK) and src kinase coordinate to regulate rapid turnover of gap junctions. Specifically, Akt phosphorylates Cx43 at S373 eliminating interaction with zona occludens-1 (ZO-1) allowing gap junctions to enlarge. Then MAPK and src phosphorylate Cx43 to initiate turnover. We integrate published data with new data to test and refine this model. Finally, we propose that differential coordination of kinase activation and Cx43 phosphorylation controls the specific routes of disassembly, e.g., annular junction formation or gap junctions can potentially "unzip" and be internalized/endocytosed into the cell that produced each connexin.

KEYWORDS:

Connexin43; Gap junction; Mitogen-activated protein kinase; Phosphorylation; Protein kinase C; Src

PMID:
24508467
PMCID:
PMC3989505
DOI:
10.1016/j.febslet.2014.01.049
[Indexed for MEDLINE]
Free PMC Article
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