title: Molecular cloning and characterization of SPAP1, an inhibitory receptor.
abstract: We have cloned a novel cell-surface protein designated SPAP1a for SH2 domain-containing phosphatase anchor protein 1a. SPAP1a belongs to the group of type I transmembrane proteins. Its extracellular domain contains a single immunoglobulin-like domain, and its intracellular segment has two immunoreceptor tyrosine-based inhibition motifs (ITIMs). We also identified two alternatively spliced products that were named SPAP1b and SPAP1c. SPAP1b contains a short intracellular part without ITIMs, while SPAP1c lacks the transmembrane segment and represents a potential soluble protein. Sequence alignment with the genomic database revealed that the SPAP1 gene contains seven exons and is localized at chromosome 1q21. PCR analyses demonstrated that SPAP1a mRNA is specifically expressed in human hematopoietic tissues including spleen, peripheral blood, and bone marrow, and it may be restricted to expression in B cells. Recombinant SPAP1a is tyrosine phosphorylated in cells upon pervanadate stimulation and tyrosine-phosphorylated SPAP1a recruits the SH2 domain containing phosphatase SHP-1, but not SHP-2. As a specific anchor protein of SHP-1, SPAP1a may have an important role in hematopoietic cell signaling.
authors.affiliation: Hematology/Oncology Division, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-6305, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Xu
authors.forename: R
authors.initials: R
authors.lastname: Zhao
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Zhao
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D018922:HL-60 Cells; D006413:Hematopoietic System / Q000166:cytology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; C422179:FCRL2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases