Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3600-5.
Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin.
Niemeyer, B. A., Bergs, C., Wissenbach, U., Flockerzi, V., Trost, C.,
["Institut fur Pharmakologie und Toxikologie der Universitat des Saarlandes, 66421 Homburg, Germany."]
["Institut fur Pharmakologie und Toxikologie der Universitat des Saarlandes, 66421 Homburg, Germany."]
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.
PMID: 11248124

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Screening
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPV6 |
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Calmodulin | Inference | Prediction | 11248124 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Validation: In vitro validation
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Assay with recombinant proteins | Reference | |||||||||
TRP channel construct | Interactor construct | |||||||||
TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
TRPV6 |
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Calmodulin | Fusion protein-pull down assay | Human | 584-725 | In vitro translation | Bovine | Full-length | E. coli | 11248124 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Characterization
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Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
TRP channel | Interactor | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPV6 |
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Calmodulin | Fluorescence probe labeling | 65 nM | 11248124 | |||||
TRPV6 |
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Calmodulin | Fusion protein-pull down assay | Human | 691-711 | Bovine | Not determined | 11248124 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Functional consequence
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TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPV6 |
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Calmodulin | Patch clamp | Inhibition | 11248124 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
