A secretion inhibitory signal transduction molecule on mast cells is another C-type lectin.
Secretion of inflammatory mediators by rat mast cells (line RBL-2H3) was earlier shown to be inhibited upon clustering a membrane glycoprotein by monoclonal antibody G63. This glycoprotein, named mast cell function-associated antigen (MAFA), was also shown to interfere with the coupling cascade of the type 1 Fc epsilon receptor upstream to phospholipase C gamma 1 activation by protein-tyrosine kinases. Here we report that the MAFA is expressed as both a monomer and a homodimer. Expression cloning of its cDNA shows that it contains a single open reading frame, encoding a 188-amino acid-long type II integral membrane protein. The 114 C-terminal amino acids display sequence homology with the carbohydrate-binding domain of calcium-dependent animal lectins, many of which have immunological functions. The cytoplasmic tail of MAFA contains a YXXL (YSTL) motif, which is conserved among related C-type lectins and is an essential element in the immunoreceptor tyrosine-based activation motifs. Finally, changes in the MAFA tyrosyl- and seryl-phosphorylation levels are observed in response to monoclonal antibody G63 binding, antigenic stimulation, and a combination of both treatments.
Guthmann
M D
MD
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Tal
M
M
Pecht
I
I
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D037102:Lectins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D037181:Lectins, C-Type; D008407:Mast Cells / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016366:Open Reading Frames; D051381:Rats; D011971:Receptors, Immunologic; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators; D014162:Transfection
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; C113413:KLRG1 protein, human; C451496:Klrg1 protein, mouse; C094696:Klrg1 protein, rat; D037102:Lectins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D015534:Trans-Activators