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-1 are components of FKBP65 immune complexes. The NH2-terminal regulatory domain of c-Raf-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-1 but not B-Raf. The activation kinetics of c-Raf-1 after v-H-RasV12 injection of Xenopus oocytes appear to correlate with FKBP65/c-Raf-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.
Coss
M C
MC
Division of Basic Science, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, Frederick, Maryland 21702-1201, USA.
Stephens
R M
RM
Morrison
D K
DK
Winterstein
D
D
Smith
L M
LM
Simek
S L
SL
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D016296:Mutagenesis; D011485:Protein Binding; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018411:Spodoptera; D022021:Tacrolimus Binding Proteins; D029867:Xenopus Proteins; D014982:Xenopus laevis
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C491676:FK506-binding protein, Xenopus; D018841:HSP90 Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D005982:Glutathione Transferase; D019908:Proto-Oncogene Proteins c-raf; D022021:Tacrolimus Binding Proteins