The Immunophilin Fkbp65 Forms an Association With the Serine/Threonine Kinase C-Raf-1

FKBP65 is a member of the FK506-binding protein class of immunophilins and is the only member reported to contain four peptidylprolyl cis-trans isomerase domains and an unrelated COOH-terminal domain, In this report, we show that the heat shock protein hsp90 and the serine/threonine protein kinase c-Raf-l are components of FKBP65 immune complexes. The NH2-terminal regulatory domain of cRaf-1 appears to be required for its interaction with FKBP65. Using GST-FKBP65 fusion protein and purified Raf proteins, we show that full-length FKBP65 can interact with c-Raf-l but not B-Raf, The activation kinetics of c-Raf-l after v-H-Ras(V12) injection of Xenopus oocytes appear to correlate with FKBP65/cRaf-1 interaction, suggesting that FKBP65 may preferentially associate with forms of c-Raf-1 that are more posttranslationally modified. The interaction of FKBP65 with the c-Raf-heat shock protein 90 heterocomplex implicates this immunophilin in signal-transduction processes. [References: 42]

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