Identification and characterization of leukocyte-associated Ig-like receptor-1 as a major anchor protein of tyrosine phosphatase SHP-1 in hematopoietic cells

Ming Jiang Xu, Runxiang Zhao, Zhizhuang Joe Zhao

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

SHP-1, an SH2 domain-containing tyrosine phosphatase, has a crucial role in hematopoiesis. Here we report that SHP-1 is associated with two major tyrosine-phosphorylated proteins in hematopoietic cells treated with the tyrosine phosphatase inhibitor, pervanadate. One of the proteins corresponds to leukocyte-associated Ig-like receptor-1 (LAIR-1), a recently cloned transmembrane protein. Molecular cloning revealed four isoforms of the protein. LAIR-1 is hyper-phosphorylated on tyrosyl residues in cells overexpressing a catalytically inactive mutant form of SHP-1 as well as in pervanadate-treated cells. An antibody against the extracellular domain of the protein also induced its tyrosine phosphorylation. Tyrosine- phosphorylated LAIR-1 specifically interacts with SHP-1 but not with SHP-2, a structurally related tyrosine phosphatase. Using site-specific mutagenesis, we demonstrated that Tyr233 and Tyr263, each embedded in an immunoreceptor tyrosine-based inhibitory motif, are responsible for tyrosine phosphorylation of LAIR-1 and recruitment of SHP-1. Both tyrosyl residues are required for SHP-1 binding. Protein kinases responsible for tyrosine phosphorylation of LAIR-1 may belong to the Src family since PP1, a Src family kinase inhibitor, significantly inhibited its phosphorylation. As a major binding protein of SHP-1 on the plasma membrane, LAIR-1 may play an important role in hematopoietic cell signaling.

Original languageEnglish (US)
Pages (from-to)17440-17446
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number23
DOIs
StatePublished - Jun 9 2000
Externally publishedYes

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Non-Receptor Type 6 Protein Tyrosine Phosphatase
Anchors
Tyrosine
Leukocytes
Phosphorylation
Phosphoric Monoester Hydrolases
Proteins
Cell signaling
Mutagenesis
src Homology Domains
src-Family Kinases
Cloning
Hematopoiesis
Molecular Cloning
Cell membranes
Site-Directed Mutagenesis
Protein-Tyrosine Kinases
Carrier Proteins
Protein Isoforms
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification and characterization of leukocyte-associated Ig-like receptor-1 as a major anchor protein of tyrosine phosphatase SHP-1 in hematopoietic cells. / Xu, Ming Jiang; Zhao, Runxiang; Zhao, Zhizhuang Joe.

In: Journal of Biological Chemistry, Vol. 275, No. 23, 09.06.2000, p. 17440-17446.

Research output: Contribution to journalArticle

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