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Discovery of Phospholamban: A Personal History
Author(s) -
KATZ ARNOLD M.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb08252.x
Subject(s) - phospholamban , lusitropy , stimulation , contractility , inotrope , phosphorylation , chemistry , endoplasmic reticulum , medicine , intracellular , endocrinology , chronotropic , biophysics , biology , biochemistry , heart rate , diastole , blood pressure
ABSTRACT: Early efforts to identify mechanisms by which sympathetic stimulation increases myocardial contractility led to studies of effects of β‐adrenergic agonists and cyclic AMP on the cardiac contractile proteins and sarcoplasmic reticulum (SR); initial positive reports, however, could not be confirmed. The discovery that cyclic AMP‐dependent protein kinases (PK‐A) mediated intracellular actions of cyclic AMP led at least four groups to test the hypothesis that phosphorylation of the cardiac SR played a role in the actions of β‐adrenergic agonists. Three of them (Wollenberger, Wray et al. , and LaRaia & Morkin) demonstrated that cardiac SR was a substrate for PK‐A phosphorylation; however, the lability of the Ca 2+ pump in these membranes made it difficult to demonstrate a functional significance of this finding. Our group, which had extensive experience in measuring SR Ca 2+ transport, began by examining the ability of PK‐A to activate the SR Ca 2+ pump “poised” at half‐saturating Ca 2+ concentrations. Our initial positive result led to the discovery that a 22,000‐dalton protein, named phospholamban by Phyllis B. Katz, mediated effects on Ca 2+ transport by the SR that could explain both the inotropic and lusitropic effects of sympathetic stimulation.