A 50 kDa protein associated with c-raf-1 and pp60^v-src is a mammalian homolog of the cell cycle control protein Cdc 37

Several oncogenic kinases including c-raf-1 and pp60v-Jrr are known to directly interact with hsp90/p50 complexes. A partial cDNA corresponding to this 5(1 kDa protein has been cloned, the amino acid sequence revealed 4X7r homology with a glycosaminoglycan-binding protein and 48% homology with dmsophila cell cycle control protein cdc37. Monoclonal and polyclonal antibodies were produced against a cleaved fusion protein that recognizes p50 (mcdc37) with a high level of specificity. These antibodies also recognize the 50 kDa protein present in c-raf-1 and pp6()v-mcomplexes. No other proteins were recognized with these antibodies suggesting that mcdc37 is a unique protein. Immunocytochemical visualization of p50 in N1H 3T3 cells indicates a primarily cytoplasmic localization around the nuclear rnembane. A survey of mcdc37 in murine tissues on a protein blot revealed the following relative levels of expression ; thymus> spleen> brain> heart> ktdney>Iiver>lung>skeletal muscle.These results link studies demonstrating complexation of certain kinases with hsp90/p50 in mammalian cells and a number of reports in yeast and tlrtisnphila demonstrating the importance of cdc37 in cell cycle and kinase function. Supported by NIEHS Grant ES-04869.