Calmodulin regulates L-selectin adhesion molecule expression and function through a protease-dependent mechanism

Julius Kahn, Bruce Walcheck, Grace I. Migaki, Mark A. Jutila, Takashi Kei Kishimoto

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

Abstract

Expression of the L-selectin adhesion molecule is rapidly down-regulated upon cell activation through proteolysis at a membrane-proximal site. Here we demonstrate that calmodulin, an intracellular calcium regulatory protein, specifically coprecipitates with L-selectin through a direct association with the cytoplasmic domain of L-selectin. Furthermore, calmodulin inhibitors disrupt L-selectin-dependent adhesion by inducing proteolytic release of L- selectin from the cell surface. The effects of the calmodulin inhibitors on L-selectin expression and function can be prevented by cotreatment with a hydroxamic acid-based metalloprotease inhibitor. Our results suggest a novel role for calmodulin in regulating the expression and function of an integral membrane protein through a protease-dependent mechanism. These findings may have broader implications for other cell surface proteins that also undergo regulated proteolysis.

Original languageEnglish (US)
Pages (from-to)809-818
Number of pages10
JournalCell
Volume92
Issue number6
DOIs
StatePublished - Mar 20 1998

Fingerprint

Dive into the research topics of 'Calmodulin regulates L-selectin adhesion molecule expression and function through a protease-dependent mechanism'. Together they form a unique fingerprint.

Cite this