title: The monocyte Fcgamma receptors FcgammaRI/gamma and FcgammaRIIA differ in their interaction with Syk and with Src-related tyrosine kinases.
abstract: There are important differences in signaling between the Fc receptor for immunoglobulin G (IgG) FcgammaRIIA, which uses the Ig tyrosine-activating motif (ITAM) within its own cytoplasmic domain, and FcgammaRI, which transmits signals by means of an ITAM located within the cytoplasmic domain of its associated gamma-chain. For example, in transfected epithelial cells and COS-1 cells, FcgammaRIIA mediates phagocytosis of IgG-coated red blood cells more efficiently than does FcgammaRI/gamma, and enhancement of phagocytosis by Syk kinase is more pronounced for FcgammaRI/gamma than for FcgammaRIIA. In addition, structure/function studies indicate that the gamma-chain ITAM and the FcgammaRIIA ITAM have different requirements for mediating the phagocytic signal. To study the differences between FcgammaRIIA and FcgammaRI/gamma, we examined the interaction of FcgammaRIIA and the FcgammaRI/gamma chimera FcgammaRI-gamma-gamma (extracellular domain-transmembrane domain-cytoplasmic domain) with Syk kinase and with the Src-related tyrosine kinases (SRTKs) Hck and Lyn in transfected COS-1 cells. Our data indicate that FcgammaRIIA interacts more readily with Syk than does FcgammaRI-gamma-gamma and suggest that one consequence may be the greater phagocytic efficiency of FcgammaRIIA compared with FcgammaRI/gamma. Furthermore, individual SRTKs affect the efficiency of phagocytosis differently for FcgammaRI-gamma-gamma and FcgammaRIIA and also influence the ability of these receptors to interact with Syk kinase. Taken together, the data suggest that differences in signaling by FcgammaRIIA and FcgammaRI-gamma-gamma are related in part to interaction with Syk and Src kinases and that individual SRTKs play different roles in FcgammaR-mediated phagocytosis.
authors.affiliation: University of Pennsylvania, School of Medicine, Hematology and Oncology Division, Biomedical Research Building II/III, Room 705, 421 Curie Blvd., Philadelphia, PA 19104, USA.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Huang
authors.forename: Sharon
authors.initials: S
authors.lastname: Hunter
authors.forename: Moo-Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Paul
authors.initials: P
authors.lastname: Chien
authors.forename: Randall G
authors.initials: RG
authors.lastname: Worth
authors.forename: Zena K
authors.initials: ZK
authors.lastname: Indik
authors.forename: Alan D
authors.initials: AD
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D010587:Phagocytosis / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017452:Receptors, IgG / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology; D000072377:Syk Kinase; D014162:Transfection; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D004792:Enzyme Precursors; C489017:FCGR1A protein, human; C080568:Fc gamma receptor IIA; C485701:Fcgr1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases