Many signalling molecules such as steroid hormone receptors and other receptors, protein kinases and phosphatases are found associated with various types of heat shock proteins, including Hsp90, Hsp70, Hsp40 and other co-chaperones. The functional role of these associations appears to be multi-faceted and the association of signalling proteins with these chaperone cohorts plays a pivotal role in initial folding and maturation of steroid hormone receptors and many kinases (e.g., Src). In addition, association with Hsp90 and its co-chaperones is critical for the stability of signalling proteins, because inhibition of Hsp90 by geldanamycin and other specific inhibitors leads to rapid ubiquitin-dependent degradation of Raf-1, Akt and other kinases that normally associate with Hsp90 [1, 2]. In fact, the anti-cancer activities of Hsp90 inhibitors could be related to the degradation and downregulation of signalling pathways that are controlled by these kinases [1, 3]. In contrast to Hsp90, which protects from degradation, an association with Hsp70 might target these proteins for rapid ubiquitination (usually via a ubiquitin ligase CHIP) followed by proteolysis .
In addition to their critical role in folding, maturation and stability of various signalling components, chaperones may be directly involved in regulation of their activities. In fact, it appears that Hsp70 and other chaperones play a regulatory role in the activation of many signalling pathways that are elicited by heat shock and other stresses.
There are multiple members of the Hsp70 protein family.