Structural Requirements for β1 Integrin-Mediated Tyrosine Phosphorylation in Human T Cells

Lisa D. Finkelstein, Pamela J. Reynolds, Stephen W. Hunt, Yoji Shimizu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The β1 integrin adhesion receptors activate signal transduction pathways that induce tyrosine phosphorylation of a variety of substrates. Increased tyrosine phosphorylation is mediated by the β1, subunit cytoplasmic domain, which consists of 46 amino acids and contains no intrinsic kinase activity. In the H9 T cell line, β1 integrin engagement leads to the increased tyrosine phosphorylation of three 105 to 115-kDa substrates that are distinct from focal adhesion kinase (FAK): HEF1 (human enhancer of filamentation 1), a protein with structural homology to p130Cas, and two novel substrates, pp105 and pp115. DNA-mediated gene transfer was used to explore the role of the β1 cytoplasmic domain in integrin-mediated tyrosine phosphorylation of HEF1, pp105, and pp115 in human T cells. Using a chimeric receptor composed of the cytoplasmic domain of the β1 integrin subunit and the extracellular and transmembrane domains of the CD2 Ag, we demonstrate that the β1 cytoplasmic domain is necessary and sufficient for inducing tyrosine phosphorylation of each of these three substrates in H9 T cells. Analysis of a series of β1 cytoplasmic domain truncations reveals that a truncation of only five amino acids from the carboxyl-terminal end of the β1 cytoplasmic domain abrogates the ability of the CD2/β1 chimera to activate tyrosine phosphorylation of HEF1, pp105, or pp115. Thus, the carboxyl-terminal five amino acids, Lys-Tyr-Glu-Gly-Lys (KYEGK), of the β1 integrin cytoplasmic domain are critical for the coordinate tyrosine phosphorylation of three non-FAK substrates in human T cells.

Original languageEnglish (US)
Pages (from-to)5355-5363
Number of pages9
JournalJournal of Immunology
Volume159
Issue number11
StatePublished - Dec 1 1997

Fingerprint

Dive into the research topics of 'Structural Requirements for β<sub>1</sub> Integrin-Mediated Tyrosine Phosphorylation in Human T Cells'. Together they form a unique fingerprint.

Cite this