The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1β subunit: Sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site

Margaret L. Hibbs, Scott Jakes, Steven A. Stacker, Robert W. Wallace, Timothy A. Springer

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210 Citations (Scopus)

Abstract

We have defined the regions of the cytoplasmic domain of the leukocyte integrin lymphocyte function-associated antigen 1 (LFA-1) that are required for active binding of its extracellular domain to intercellular adhesion molecule 1 (ICAM-1). The NH2-terminal 28 amino acids in the cytoplasmic domain are dispensable, but a segment of 5 amino acids including three contiguous threonines (758-760) and Phe 766 in the COOH-terminal third of the cytoplasmic domain are required for binding to ICAM-1. Mutation and phosphoamino acid analysis show that Set 756 is the major residue phosphorylated in response to phorbol ester. Furthermore, multiple mutations demonstrate that serine phosphorylation can be dissociated from phorbol ester-stimulated binding of LFA-1 to ICAM-1. The sites we have defined are previously unremarked, are well conserved in the β1, β3, and β7 integrin subunits, and may be of broad importance in regulating adhesiveness of integrins.

Original languageEnglish
Pages (from-to)1227-1238
Number of pages12
JournalJournal of Experimental Medicine
Volume174
Issue number5
DOIs
Publication statusPublished - 1 Nov 1991
Externally publishedYes

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