PMID: 7520912Sep 2, 1994Paper

The native v-Raf.hsp90.p50 heterocomplex contains a novel immunophilin of the FK506 binding class.

The Journal of Biological Chemistry
L F StancatoW B Pratt

Abstract

We have recently reported that v-Raf forms a native heterocomplex with rat heat shock protein (hsp) 90 and a 50-kDa phosphoprotein (p50) in stably transfected 3Y1 fibroblasts (Stancato, L. F., Chow, Y-H., Hutchison, K. A., Perdew, G. H., Jove, R., and Pratt, W. B. (1993) J. Biol. Chem. 268, 21711-21716). Several members of the nuclear receptor family exist in heterocomplexes containing hsp90 and various members of the immunophilin protein family, including hsp56, an immunophilin of the FK506 binding class (Pratt, W. B. (1993) J. Biol. Chem. 268, 21455-21458). In this work, we have asked if Raf is also associated with an immunophilin. We have immunoadsorbed v-Raf from stably transfected rat 3Y1 fibroblasts and show that the immunoadsorbed v-Raf.hsp90.p50 heterocomplex binds the immunosuppressant drug [3H]FK506. The binding is of high affinity (KD 82 nM) and specific in the sense that it is competed by nonradioactive FK506 and rapamycin but not by cyclosporin A. The [3H]FK506 binding activity is eliminated when the heterocomplex proteins are dissociated from v-Raf. Using the 22W mutant of c-Raf in which the NH2-terminal half has been deleted, we show that the catalytic domain of the kinase is sufficient for the immunophilin assoc...Continue Reading

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