QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nollen, E. A. A. Articles by Morimoto, R. I. Search for Related Content PubMed PubMed Citation Articles by Nollen, E. A. A. Articles by Morimoto, R. I.

Chaperoning signaling pathways: molecular chaperones as stress-sensing `heat shock' proteins

Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA

View larger version (9K): [in a new window]   Fig. 1. Schematic and linear representation of the domain structure and co-chaperone-binding sites of Hsp70 and Hsp90. The amino-acid residue numbers, domains and co-chaperone-binding sites are indicated. (A) Domain structure of human Hsp70. The C-terminal EEVD motif is characteristic for cytosolic Hsp70s and is involved in binding of TPR-domain-containing proteins. (B) Domain structure of human Hsp90. The C-terminal MEEVD motif is involved in binding of TPR-domain-containing proteins. Binding sites of co-chaperones on Hsp90 are a composite of sites of interaction for mammalian and yeast Hsp90 [adapted from previous reports (Chen and Smith, 1998; Grammatikakis et al., 1999; Young et al., 2001)].

View larger version (12K): [in a new window]   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).

View larger version (11K): [in a new window]   Fig. 3. A model for chaperone and co-chaperone interactions with nuclear hormone receptors. Chaperones and co-chaperones play a role in the maturation and inactivation of nuclear hormone receptors. During maturation, Hsp70 (70) and Hsp(40) bind to the hormone-binding domain (HBD) of the receptor (in white), which is followed by the association of Hop and Hsp90 (90). Maturation of the aporeceptor complex is completed by dissociation of Hsp40, Hsp70 and Hop followed by association of p23 (23) and one of the immunophilins (I). Hormone binding and dissociation of Hsp90, p23 and the immunophilin changes the conformation of the receptor, which then translocates to the nucleus and activates transcription. Bag1 can associate with the activated receptor and inhibit the activities of the receptor for which it requires its Hsp70-binding domain. AD, activation domain; DB, DNA-binding domain (see text for References).