Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 2 March 2004
Vol. 2004, Issue 222, p. tw77
[DOI: 10.1126/stke.2222004TW77]

EDITORS' CHOICE

CALCIUM REGULATION RACK1-Promoted Calcium Release

The protein RACK1 (receptor for activated C kinase 1) binds active forms of protein kinase C (PKC) and is thought to function as a scaffold or adaptor protein in various signaling pathways. Patterson et al. discovered a new role for RACK1 when it showed up in a two-hybrid screen for proteins interacting with fragments of the inositol 1,4,5-trisphosphate receptor (IP3R). The authors went on to show the interaction of the full-length endogenous proteins in vivo in PC12 cells. Furthermore, RACK1 appeared to increase the affinity of IP3 for the IP3R in preparations of membranes from rat brain or in microsomal membranes from COS7 cells. In multiple cell types from various species, depletion of RACK1 with siRNA reduced Ca2+ release in response to agonists (including uridine triphosphate, carbachol, and vasopressin) that normally stimulate IP3-dependent Ca2+ release from intracellular stores. Though the IP3R is thought to be a substrate for PKC, pharmacological inhibition of PKC did not affect basal or RACK1-stimulated Ca2+ release in response to activation of purinergic receptors in PC12 cells. RACK1 has been implicated in neuronal physiology and pathology, and modulation of Ca2+ release through IP3Rs will now need to be considered along with other potential mechanisms of RACK1 action.

R. L. Patterson, D. B. van Rossum, R. K. Barrow, S. H. Snyder, RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release. Proc. Natl. Acad. Sci. U.S.A. 101, 2328-2332 (2004). [Abstract] [Full Text]

Citation: RACK1-Promoted Calcium Release. Sci. STKE 2004, tw77 (2004).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882