Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin.

A finely tuned Ca(2+) signaling system is essential for cells to transduce extracellular stimuli, to regulate growth, and to differentiate. We have recently cloned CaT-like (CaT-L), a highly selective Ca(2+) channel closely related to the epithelial calcium channels (ECaC) and the calcium transport protein CaT1. CaT-L is expressed in selected ...
exocrine tissues, and its expression also strikingly correlates with the malignancy of prostate cancer. The expression pattern and selective Ca(2+) permeation properties suggest an important function in Ca(2+) uptake and a role in tumor progression, but not much is known about the regulation of this subfamily of ion channels. We now demonstrate a biochemical and functional mechanism by which cells can control CaT-L activity. CaT-L is regulated by means of a unique calmodulin binding site, which, at the same time, is a target for protein kinase C-dependent phosphorylation. We show that Ca(2+)-dependent calmodulin binding to CaT-L, which facilitates channel inactivation, can be counteracted by protein kinase C-mediated phosphorylation of the calmodulin binding site.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, CHO Cells, Calcium, Calcium Channels, Calcium-Binding Proteins, Calmodulin, Cell Line, Cricetinae, Humans, Molecular Sequence Data, Phosphorylation, Protein Kinase C, Recombinant Fusion Proteins, TRPV Cation Channels
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 13, 2001
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