Fig. 2. A model for chaperone and co-chaperone interactions with Raf-1. Chaperones and co-chaperones play a role in the maturation, activation and inactivation of Raf-1. During maturation Cdc37 (37) and Hsp90 (90) bind to the regulatory and kinase domains of Raf-1 (in white) and keep it in an inactive conformation. Dissociation of Cdc37 and Hsp90 followed by association of Ras and/or Bag1 leads to a conformational change of Raf-1 that enables its activation. Sequestration of Bag1 by Hsp70 (70) and association of 14-3-3 leads to the inactivation of Raf-1. Raf-1 co-associating and regulatory proteins other than Ras, chaperones or co-chaperones are omitted from the model for the sake of simplicity (see text for details and References).