Ligand binding specificities and signal transduction pathways of Fc gamma receptor IIc isoforms: the CD32 isoforms expressed by human NK cells.
We recently reported that human NK cells express, in addition to CD16 [Fcgamma receptor (FcgammaR) IIIA], a second type of FcgammaR, namely CD32 (FcgammaRII). Molecular characterization of CD32 transcripts expressed by highly purified NK cells revealed that they predominantly express products of the FcgammaRIIC gene. Using stable Jurkat transfectants we have analyzed the functional properties of two FcgammaRIIc-specific isoforms isolated from NK cells, namely FcgammaRIIc1 and FcgammaRIIc3, which differ in their cytoplasmic tails. The ligand binding specificity for both murine and human IgG isotypes was found to be similar to that observed for FcgammaRIIb isoforms. Immunoprecipitation studies of FcgammaRIIc isoforms expressed in Jurkat cells revealed a protein of around 40 kDa for FcgammaRIIc1, and a protein of around 32 kDa for FcgammaRIIc3. Signal transduction studies performed on FcgammaRIIc1-expressing Jurkat cells indicated that this molecule is functional, i. e. capable of Ca2+ mobilization and activation of Lck, Zap-70 and Syk protein tyrosine kinases, although the CD3 zeta chain was not found to functionally associate with FcgammaRIIc1. In contrast, FcgammaRIIc3 transfectants showed an impaired ability of this molecule to mobilize Ca2+, but activation of Lck was detected following activation via FcgammaRIIc3. These studies demonstrate the functional activity of FcgammaRIIc isoforms and suggest that the presence of CD32, in addition to CD16, on NK cells may have functional relevance.
Metes
D
D
Department of Surgery, University of Pittsburgh, Pittsburgh, USA.
Manciulea
M
M
Pretrusca
D
D
Rabinowich
H
H
Ernst
L K
LK
Popescu
I
I
Calugaru
A
A
Sulica
A
A
Chambers
W H
WH
Herberman
R B
RB
Morel
P A
PA
D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D000939:Epitopes / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000737:chemistry / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells
D015703:Antigens, CD; D003432:Cross-Linking Reagents; D000939:Epitopes; C080572:Fc gamma receptor IIC; D008024:Ligands; D020033:Protein Isoforms; D017452:Receptors, IgG; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)