RACK1 is a BK Ca channel binding protein

• Published in: American Journal of Physiology: Cell Physiology 2007-04, Vol.292 (4), p.C1459-C1466
• Main Authors: Isacson, Christina Kaldany, Lu, Qing, Karas, Richard H., Cox, Daniel H.
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00322.2006

The large conductance calcium-activated potassium channel, or BK Ca channel, plays an important feedback role in a variety of physiological processes, including neurotransmitter release and smooth muscle contraction. Some reports have suggested that this channel forms a stable complex with regulators of its function, including several kinases and phosphatases. To further define such signaling complexes, we used the yeast two-hybrid system to screen a human aorta cDNA library for proteins that bind to the BK Ca channel's intracellular, COOH-terminal “tail”. One of the interactors we identified is the protein receptor for activated C kinase 1 (RACK1). RACK1 is a member of the WD40 protein family, which also includes the G protein β-subunits. Consistent with an important role in BK Ca -channel regulation, RACK1 has been shown to be a scaffolding protein that interacts with a wide variety of signaling molecules, including cSRC and PKC. We have confirmed the interaction between RACK1 and the BK Ca channel biochemically with GST pull-down and coimmunoprecipitation experiments. We have observed some co-localization of RACK1 with the BK Ca channel in vascular smooth muscle cells with immunocytochemical experiments, and we have found that RACK1 has effects on the BK Ca channel's biophysical properties. Thus RACK1 binds to the BK Ca channel and it may form part of a BK Ca -channel regulatory complex in vascular smooth muscle.