The major SHP-1-binding, tyrosine-phosphorylated protein in macrophages is a member of the KIR/LIR family and an SHP-1 substrate.
The SH2 domain-containing cytoplasmic protein tyrosine phosphatase, SHP-1, negatively regulates hematopoietic cell signaling. SHP-1 is associated with a tyrosine phosphorylated, plasma membrane-spanning glycoprotein, pp130, in colony stimulating factor-1 stimulated or unstimulated macrophages. This association is phosphotyrosine dependent and is mediated by the amino-terminal SH2 domain of SHP-1. pp130 behaves as a substrate of SHP-1 in vitro and is hyperphosphorylated on tyrosine in SHP-1 deficient macrophages from viable-motheaten mice. Co-immunoprecipitation data indicate that pp130 is the product of the mouse p91/PIR-B gene that encodes a member of the killer cell inhibitory receptor (KIR)/leukocyte immunoglobulin-like receptor (LIR) family. By analogy to the KIRs, p91/PIR-B may represent a novel class of macrophage receptors which act to suppress macrophage activation. These observations identify SHP-1 interactions with and regulation of p91/PIR-B as a potential mechanism for inhibiting the signaling cascades linking extracellular stimuli to macrophage activation and/or development.
Berg
K L
KL
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Carlberg
K
K
Rohrschneider
L R
LR
Siminovitch
K A
KA
Stanley
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D047908:Intracellular Signaling Peptides and Proteins; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000502:physiology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D018909:src Homology Domains
D015703:Antigens, CD; D047908:Intracellular Signaling Peptides and Proteins; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D009687:Nuclear Proteins; D010750:Phosphoproteins; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D054340:Receptors, KIR; C095383:nucleolar phosphoprotein p130; D019000:Phosphotyrosine; 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; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases