Cell Growth & Differentiation, Vol 9, Issue 1 13-21, Copyright © 1998 by American Association of Cancer Research

ARTICLES

Cdc2-mediated phosphorylation of the gap junction protein, connexin43, during mitosis

MY Kanemitsu, W Jiang and W Eckhart
Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, San Diego, California 92186, USA. kanemitsu@AXP1.salk.edu

As cells enter mitosis, gap junctional communication with neighboring cells decreases (H. Xie et al., J. Cell Biol., 137: 203-210, 1997). Phosphorylation of the gap junction protein, connexin43 (Cx43), has been implicated in reducing junctional permeability. Cx43 contains p34cdc2 phosphorylation consensus sites in its COOH-terminal region. Accordingly, we examined the role of p34cdc2/cyclin B in Cx43 phosphorylation. Purified p34cdc2/cyclin B, or p34cdc2/cyclin B complex immunoprecipitated from mitotic cells, phosphorylated GSTCx43 in vitro. The synthetic peptide, SDPYHATTGPLSPSKDCGSPK, corresponding to amino acids 241-264 of Cx43, was also phosphorylated by p34cdc2/cyclin B in vitro. Sites phosphorylated in vitro were phosphorylated in vivo. Butyrolactone I, an inhibitor of cdc2 kinase, inhibited increases in Cx43 phosphorylation during mitosis. We conclude that phosphorylation of Cx43 by p34cdc2/cyclin B may contribute to the increased Cx43 phosphorylation and reduced gap junctional communication observed during mitosis.

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