Open AccessCalcium‐Independent Activation of Adenylate Cyclase by Calmodulin
Author(s) -
KILHOFFER MarieClaude,
COOK G. HOPE,
WOLFF J.
Publication year - 1983
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1983.tb07423.x
Subject(s) - egta , calmodulin , cyclase , adenylate kinase , calcium , chemistry , chelation , stimulation , biochemistry , activator (genetics) , biophysics , medicine , endocrinology , biology , enzyme , inorganic chemistry , receptor , organic chemistry
Adenylate cyclase of Bordetella pertussis is stimulated by calmodulin by two distinct interactions. At low activator concentrations (∼ 1 nM) the process is Ca 2+ ‐dependent (i.e. inhibited by EGTA added before calmodulin). High activator concentrations (∼ 0.1–10 μM) stimulate adenylate cyclase also in the presence of EGTA, an effect not accounted for by residual Ca 2+ or low concentrations of Ca · calmodulin, which thus appears to be due to calcium‐free calmodulin. Some calmodulin dose‐response curves show both phases of stimulation, separated by a plateau of activity, and half‐maximal activating concentrations differ by 100–300‐fold. Both effects are on the V and not the K m for ATP and are not mimicked by 10 5 ‐fold greater concentrations of parvalbumin or by various polyanions. In addition, adenylate cyclase stimulation at high calmodulin concentrations is greater in the presence of EGTA than in its absence. This enhancement is also produced by 1,10‐phenanthroline and 8‐hydroxyquinoline but not by non‐chelating isomers. These compounds are poor Ca 2+ chelators, stimulate at any calmodulin concentration (unlike EGTA), and suggest regulation of this adenylate cyclase by a second metal ion.