SPAP2, an Ig family receptor containing both ITIMs and ITAMs

Ming jiang Xu, Runxiang Zhao, Hongxi Cao, Zhizhuang Joe Zhao

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

This study reports cloning and characterization of SPAP2, a novel transmembrane protein. The extracellular portion of SPAP2 contains six immunoglobulin-like domains and its intracellular segment has two immunoreceptor tyrosine-based activation motifs (ITAMs) and two immunoreceptor tyrosine-based inhibition motifs (ITIMs). We also identified four alternatively spliced products. Sequence alignment with the genomic database revealed that the SPAP2 gene contains 16 exons and is localized at chromosome 1q21. PCR analyses demonstrated that SPAP2 mRNA is expressed in restricted human tissues including the kidney, salivary gland, adrenal gland, uterus, and bone marrow. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2. Finally, recruitment of SHP-1 to the tyrosine-phosphorylated ITIMs led to a marked activation of the enzyme.

Original languageEnglish (US)
Pages (from-to)1037-1046
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume293
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

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Immunoreceptor Tyrosine-Based Inhibition Motif
Immunoreceptor Tyrosine-Based Activation Motif
Tyrosine
Chemical activation
src Homology Domains
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Enzyme Activation
Sequence Alignment
Adrenal Glands
Site-Directed Mutagenesis
Salivary Glands
Protein-Tyrosine Kinases
Uterus
Organism Cloning
Exons
Chromosomes
Bone Marrow
Databases
Mutagenesis
Kidney

Keywords

  • Ig family protein
  • ITAM
  • ITIM
  • Tyrosine kinase
  • Tyrosine phosphatase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

SPAP2, an Ig family receptor containing both ITIMs and ITAMs. / Xu, Ming jiang; Zhao, Runxiang; Cao, Hongxi; Zhao, Zhizhuang Joe.

In: Biochemical and Biophysical Research Communications, Vol. 293, No. 3, 2002, p. 1037-1046.

Research output: Contribution to journalArticle

Xu, Ming jiang ; Zhao, Runxiang ; Cao, Hongxi ; Zhao, Zhizhuang Joe. / SPAP2, an Ig family receptor containing both ITIMs and ITAMs. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 293, No. 3. pp. 1037-1046.
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