SPAP2, an Ig family receptor containing both ITIMs and ITAMs.
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.
Xu
Ming-jiang
MJ
Hematology/Oncology Division, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232-6305, USA.
Zhao
Runxiang
R
Cao
Hongxi
H
Zhao
Zhizhuang Joe
ZJ
D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution; D018909:src Homology Domains
C457775:FCRL3 protein, human; D007136:Immunoglobulins; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases