Understanding the crosstalk between receptor and non-receptor tyrosine kinase signal transduction pathways and Cx43 gap junctional communication
Mitra, Siddhartha S.
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The regulation of communication through gap junction channels consistently correlates with regulation of cellular proliferation and differentiation. In fact one of the initial functions attributed to gap junction channels was the passage of growth regulatory signals. This hypothesis was supported by the negative correlation between intercellular communication and the rate of cell growth in many cell lines. Decreases in gap junctional coupling have consistently been associated with the induction of rapid or synchronous cell division in both normal and pathological conditions. Unfortunately, the precise role of junctional communication in growth regulation still remains a mystery. Here we have attempted to explore the complex crosstalk which occurs between cell surface receptor and non-receptor tyrosine kinases and Cx43 gap junctional communication. Cells transformed by the v-src oncogene have offered a particularly useful system for investigation of the mechanisms) that can mediate both acute and chronic closure of gap junction channels. Using the Xenopus oocyte expression system we have dissected multiple signaling pathways by which the initial (acute) closure of pre-formed Cx43 channels in response to v-src occurs. In the second study, using biochemical and fluorescence microscopic techniques we have attempted to investigate the raison d'étre for the acute inhibition of junctional communication during mitogenic stimuli.