The connexins are a group of gap junction proteins which form a hexamer to compose a connexon. Clusters of connexons form a gap junction through which low molecular weight proteins may diffuse from cell to cell. Several mammalian cells with malignant phenotypes exhibit decreased connexin expression and gap junction communication. In Src transformed cells, there is a decrease in gap junctional communication, which appears to be associated with tyrosine phosphorylation of connexin 43. Activated c-Src phosphorylates the C-terminal tail of connexin 43 on Tyr 265, resulting in a stable interaction between both proteins, which leads to inhibition of gap junctional communication. In addition to tyrosine phosphorylation, connexin 43 has also been shown to be phosphorylated on serine in the absence of Src kinases and on both serine and tyrosine in cells expressing Src kinases, such as c-Src and/or pp60v-Src. In human vascular endothelial cells, connexin 43 is posttranslationally modified during mitosis. Mitosis-specific phosphorylation of connexin 43 correlates with the transient loss of gap junction intercellular communication and redistribution of connexin 43.