MAT-8, A NOVEL PHOSPHOLEMMAN-LIKE PROTEIN EXPRESSED IN HUMAN BREAST-TUMORS, INDUCES A CHLORIDE CONDUCTANCE IN XENOPUS OOCYTES

We recently identified a novel 8-kDa transmembrane protein, Mat-8, tha t is expressed in a subset of murine breast tumors. We have now cloned a cDNA encoding the human version of Mat-8 and show that it is expres sed both in primary human breast tumors and in human breast tumor cell lines. The extracellular and transmembrane domains of Mat-8 are homol ogous to those of phospholemman (PLM), the major plasmalemmal substrat e for cAMP-dependent protein kinase and protein kinase C in several di fferent tissues, PLM, which induces chloride currents when expressed i n Xenopus oocytes, contains consensus phosphorylation sites for both c AMP-dependent protein kinase A and protein kinase C in its cytoplasmic domain. In contrast, the cytoplasmic domain of Mat-8 contains no such consensus phosphorylation sites and is, in fact, unrelated to the cyt oplasmic domain of PLM, RNA blot analysis reveals that Mat-8 and PLM e xhibit distinct tissue-specific patterns of expression. We show that e xpression of Mat-8 in Xenopus oocytes induces hyperpolarization-activa ted chloride currents similar to those induced by PLM expression, Thes e findings suggest that Mat-8 and PLM, the products of distinct genes, are related proteins that serve as Cl- channels or Cl- channel regula tors but have different roles in cell and organ physiology.