Characterization and expression of the gene for the human Fc receptor gamma subunit. Definition of a new gene family.
The high affinity IgE receptor, Fc epsilon RI, is one of the key molecules involved in allergic reactions. It is a tetrameric complex (alpha beta gamma 2). The gamma chains from Fc epsilon RI are also subunits of other Fc receptors. We have isolated, characterized, and sequenced the gene for the human gamma chain of Fc epsilon RI. It consists of five exons and spans 4 kilobases. The leader sequence is encoded by two exons, the second of which also contains the short extracellular domain, the hydrophobic transmembrane region, and the beginning of the cytoplasmic tail. Three short exons encode the remaining of the polypeptide and the 3'-untranslated flanking sequence. The transcription initiation sites have been mapped. Comparison between the gene structures of the gamma chain of the Fc receptor and of the zeta chain of the T-cell receptor indicates that these genes have evolved from a common ancestor by duplication and that they define a new gene family. In addition to being localized on the same chromosome, both genes show an analogous organization of their exons. A high level of homology is found in three of their respective exons, and the splice sites between them are identical. Furthermore, gamma and zeta chains are essential for surface expression of their respective receptors. Therefore, gamma chains of Fc receptors and zeta chains of T-cell receptors may also define a new family of functionally related polypeptides. Expression studies in COS cells show that the human gamma chain alone is sufficient to achieve expression of the human alpha chain on the cell surface, whereas both beta and gamma chains are required for the surface expression of the rodent alpha chain.
Küster
H
H
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Thompson
H
H
Kinet
J P
JP
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics; D000943:Antigens, Differentiation / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D001483:Base Sequence; D001491:Basophils / Q000276:immunology; D003001:Cloning, Molecular; D015870:Gene Expression; D015723:Gene Library; D015698:Genomic Library; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011961:Receptors, Fc / Q000235:genetics*; D017455:Receptors, IgE; D017452:Receptors, IgG; D015183:Restriction Mapping; D014158:Transcription, Genetic
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG