The IREM-1 (CD300f) inhibitory receptor associates with the p85alpha subunit of phosphoinositide 3-kinase.
The immune receptor expressed by myeloid cell 1 (IREM-1) (CD300f) inhibitory receptor displays five cytoplasmic tyrosine residues, two of them (Y205 and Y249) fit with ITIMs, whereas Y236 and Y263 constitute putative binding sites for PI3K. In the present study, immunoprecipitation analysis revealed that both the p85alpha subunit of PI3K and Src homology region 2 domain-containing phosphatase-1 could be recruited by IREM-1 in transfected cells as well as in the U937 monocytic leukemia cells, which constitutively express the receptor. By assaying the ability of different IREM-1 mutants to regulate the secretion of beta-hexosaminidase induced via FcRepsilonI in rat basophilic leukemia cells, both Y205 and Y249 appeared crucial for IREM-1-mediated inhibition. Remarkably, engagement of an IREM-1 mutant (Y(205,249,284)F), which did not recruit Src homology region 2 domain-containing phosphatase-1 and lost its inhibitory function, induced rat basophilic leukemia cell degranulation. This effect was dependent on the recruitment of PI3K, requiring the integrity of Y236 and Y263, and was blocked by PI3K inhibitors (i.e., wortmannin and LY-294002). Altogether, these data reveal a putative functional duality of the IREM-1 myeloid cell receptor.
Alvarez-Errico
Damiana
D
Molecular Immunopathology Unit, Department de Ciéncies Experimentals i de la Salut, Universitat Pompeu Fabra, Doctor Aiguader 80, 08003 Barcelona, Spain.
Sayós
Joan
J
López-Botet
Miguel
M
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D000954:Antigens, Surface; D051380:GRB2 Adaptor Protein; D008562:Membrane Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D054645:Protein Phosphatase 1; D021122:Protein Subunits; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D051057:Proto-Oncogene Proteins c-akt; D017455:Receptors, IgE; D014443:Tyrosine; C444139:CD300C protein, human