Trypsin cleavage of the β1-adrenergic receptor

Abstract

Current concepts regarding the molecular basis for β1AR responses derive from literature predicated on the assumption that β1ARs signal exclusively as full-length receptor proteins. However, we recently showed that β1ARs accumulate as both full-length and N-terminally truncated forms in cardiomyocytes and other cell types and that these distinct β1AR species evoke distinct signaling responses. This manuscript provides novel evidence that β1-adrenergic receptors can be cleaved by trypsin (and presumably other inflammatory serine proteases) and that cell surface β1AR cleavage constitutes a heretofore unrecognized mechanism to alter catecholamine-dependent signaling responses.