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We are studying the role of viral oncogenes in normal and neoplastic cell growth regulation, including the role of phosphorylation in regulation of gap junctional intercellular communication (GJIC).
Gap junctions are intercellular channels that allow cells to communicate by exchanging cytosolic molecules such as ions, second messengers and small metabolites. Gap junctions are formed by proteins called connexins, which assemble into hexameric structures that span the plasma membranes of two adjacent cells, allowing direct intercellular signaling. These channels have been implicated in synchronous activity between excitable cells, control of pattern formation during development, and cell proliferation. GJIC is greatly reduced in cells transformed by a variety of oncogenes, including v-src and polyoma middle T antigen (MT). Restoration of GJIC suppresses the transformed phenotype, suggesting that connexins may act as tumor suppressor genes. Several lines of evidence suggest that GJIC is regulated by phosphorylation of connexins. We are using mutated forms of Cx43, lacking phosphorylation sites, to study the role of connexin 43 in GJIC, cell growth regulation, and neoplastic cell transfomation by MT and Src.