Epidermal growth factor disrupts gap-junctional communication and induces phosphorylation of connexin43 on serine.
Growth factors regulate cellular proliferation and differentiation by activating plasma membrane tyrosine kinase receptors and triggering a cascade of events mediated by intracellular signaling proteins. The mechanism underlying growth factor modification of cellular functions, such as gap-junctional communication (gjc), has not been established clearly. Addition of epidermal growth factor (EGF) to T51B rat liver epithelial cells resulted in the rapid activation of EGF receptor tyrosine kinase activity followed by a transient dose-dependent disruption of gjc. This change did not result from the gross disturbance of membrane gap junction plaques as measured by immunofluorescence microscopy, but instead correlated with markedly elevated phosphorylation of the connexin43 (cx43) gap junction protein, a profound shift to predominantly phosphorylated forms of cx43, and the appearance of a novel phosphorylated cx43 protein. These changes in cx43 phosphorylation involved only serine residues. On restoration of gjc, these alterations in cx43 phosphorylation reverted to the pre-EGF treatment state. Both events were inhibited by the serine/threonine protein phosphatase inhibitor, okadaic acid. Therefore, unlike the case for pp60v-src, EGF-induced disruption of gjc is not associated with tyrosine phosphorylation of cx43, but instead may result from phosphorylation of cx43 by activated intracellular signaling serine protein kinase(s).
Lau
A F
AF
Molecular Oncology Program, University of Hawaii, Manoa, Honolulu 96813.
Kanemitsu
M Y
MY
Kurata
W E
WE
Danesh
S
S
Boynton
A L
AL
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D017630:Connexins; D004815:Epidermal Growth Factor / Q000502:physiology*; D007365:Intercellular Junctions / Q000378:metabolism* / Q000502:physiology; D008099:Liver / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D012694:Serine / Q000378:metabolism*
D017630:Connexins; D008565:Membrane Proteins; D012694:Serine; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases