A 50 kilodalton protein associated with raf and pp60(v-src) protein kinases is a mammalian homolog of the cell cycle control protein cdc37

Biochemistry. 1997 Mar 25;36(12):3600-7. doi: 10.1021/bi9612529.


Several oncogenic protein kinases including c-raf-1 and pp60(v-src) are known to directly interact with the 90 kDa heat shock protein (hsp90)/p50 complexes. Using a monoclonal antibody to detect p50 during a purification scheme, p50 was purified to homogeneity. Internal amino acid sequence information was obtained and used to clone a partial cDNA. Comparison of the p50 sequence to other cloned proteins revealed 89% homology with a glycosaminoglycan-binding protein and 54% homology with Drosophila cell cycle control protein (cdc) 37. Monoclonal and polyclonal antibodies were produced against a cleaved fusion protein that recognizes p50 with a high level of specificity. These antibodies recognize the 50 kDa protein present in c-raf-1 and pp60(v-src) complexes. No other proteins were recognized with these antibodies suggesting that p50 is a unique protein. Immunocytochemical visualization of p50 in NIH 3T3 cells indicates a primarily cytoplasmic localization around the nuclear membrane. A survey of p50 expression in murine tissues on a protein blot revealed the following relative levels of expression; thymus > spleen > brain > heart > kidney > liver > 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 Drosophila, demonstrating the importance of cdc37 in cell cycle and kinase function.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Blotting, Western
  • Cell Cycle Proteins / chemistry*
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Drosophila
  • Drosophila Proteins*
  • Fluorescent Antibody Technique, Indirect
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / isolation & purification
  • Immunoglobulin M
  • Mice
  • Molecular Chaperones*
  • Molecular Sequence Data
  • Molecular Weight
  • Oncogene Protein pp60(v-src) / chemistry*
  • Polymerase Chain Reaction
  • Protein-Serine-Threonine Kinases / chemistry*
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins c-raf


  • Antibodies, Monoclonal
  • Cdc37 protein, Drosophila
  • Cdc37 protein, mouse
  • Cell Cycle Proteins
  • Drosophila Proteins
  • Heat-Shock Proteins
  • Immunoglobulin M
  • Molecular Chaperones
  • Proto-Oncogene Proteins
  • Oncogene Protein pp60(v-src)
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf