Selective Activation and Inhibition of Calmodulin‐Dependent Enzymes by a Calmodulin‐Like Protein Found in Human Epithelial Cells

Abstract

A calmodulin‐like protein, which is identical in size and 85% identical to vertebrate calmodulin, was recently identified by ‘subtractive hybridization’ comparison of transcripts expressed in normal versus transformed human mammary epithelial cells. Unlike the ubiquitous distribution of calmodulin, calmodulin‐like protein expression is restricted to certain epithelial cells, and appears to be modulated during differentiation. In addition, calmodulin‐like protein levels are often significantly reduced in malignant tumor cells as compared to corresponding normal epithelial cells. The current studies compare calmodulin‐like protein functions with those of calmodulin. We find that calmodulin‐like protein activation of multifunctional Ca2+/calmodulin‐dependent protein kinase II (calmodulin kinase II) is equivalent to activation by calmodulin, but that four other calmodulin‐dependent enzymes, cGMP phosphodiesterase, calcineurin, nitric‐oxide synthase, and myosin‐light‐chain kinase, display much weaker activation by calmodulin‐like protein than by calmodulin. In the case of myosin‐light‐chain kinase, calmodulin‐like protein competitively inhibits calmodulin activation of the enzyme with a Ki value of 170 nM. Thus, calmodulin‐like protein may have evolved to function as a specific agonist of certain calmodulin‐dependent enzymes, and/or as a specific competitive antagonist of other calmodulin‐dependent enzymes. Copyright © 1994, Wiley Blackwell. All rights reserved