Connexin 43 in LA-25 cells with active v-src is phosphorylated on Y247, Y265, S262, S279/282, and S368 via multiple signaling pathways.
Modulation of gap junction structures and gap junctional communication is important in maintaining tissue homeostasis and can be controlled via phosphorylation of connexin 43 (Cx43) through several different signaling pathways. Transformation of cells by v-src has been shown to down-regulate gap junction communication coincident with an increase in tyrosine phosphorylation on Cx43. Activation of mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) also lead to down-regulation via phosphorylation on specific serine residues. Using phosphospecific anti-Cx43 antibodies generated by the authors' laboratory to specific tyrosines (src substrates) and serine residues (MAPK and PKC substrates) to probe LA-25 cells (which express temperature-sensitive v-src), the authors show that distinct tyrosine and serines residues are phosphorylated in response to v-src activity. They show that tyrosine phosphorylation appears to occur predominantly in gap junction plaques when src is active. In addition, src activation led to increased phosphorylation of apparent MAPK and PKC sites in Cx43. These results indicate all three signaling pathways could contribute to gap junction down-regulation during src transformation in LA-25 cells.
Solan
Joell L
JL
Molecular Diagnostics Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Lampe
Paul D
PD
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D018031:Connexin 43; D014443:Tyrosine; D012694:Serine; D015688:Oncogene Protein pp60(v-src)