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H Küster

Publications and source records attributed to H Küster.

4 recordsLinked to original sources
PubMed1992

The gene and cDNA for the human high affinity immunoglobulin E receptor beta chain and expression of the complete human receptor.

The high affinity IgE receptor (Fc epsilon RI) is a tetrameric hetero-oligomer composed of an alpha chain, a beta chain, and two disulfide-linked gamma chains. The beta chain contains four transmembrane (TM) segments and long cytoplasmic domains that are thought to play an important role in intracellular signaling. We now report the structural characterization and the sequence of the complete human beta gene and cDNA. The gene spans approximately 10 kilobases and contains seven exons. There is a single transcription initiation site preceded by a TATA box. The first exon codes for the 5'-untranslated region and a portion of the N-terminal cytoplasmic tail. TM-1 is encoded in exons 2 and 3, TM-2 in exons 3 and 4, TM-3 in exon 5, and TM-4 in exon 6. The seventh and final exon encodes the end of the C-terminal cytoplasmic tail and the 3'-untranslated sequence. The human beta gene appears to be a single copy gene. Two corresponding transcripts, detected as a doublet around 3.9 kilobases, are present in cells of mast cell and basophil lineage from different individuals, but not in the other hematopoietic cells tested here. The human beta protein is homologous to rodent beta. The consensus amino acid sequences of human, mouse, and rat beta show 69% identical residues. Analysis of the surface expression of transfected receptors indicates that human alpha gamma and alpha beta gamma complexes are expressed with comparable efficiency. Human beta interacts with human alpha more efficiently than does rat beta, and both rat and mouse beta interact with their corresponding alpha more efficiently than does human beta, demonstrating a species specificity of the alpha/beta interaction.

Amino Acid Sequence↗
PubMed1991

The high-affinity receptor for immunoglobulin E: a target for therapy of allergic diseases.

The high-affinity receptor for IgE (Fc epsilon RI) on mast cells and basophils is a tetrameric complex, alpha beta gamma 2. Here we summarize the latest developments on the structure and function of this receptor. By genetic transfer, we have engineered a cell line secreting substantial amounts of a peptide containing exclusively the extracellular domain of the alpha-subunit. This domain by itself is sufficient to mediate high-affinity binding of IgE. Glycosylation and the presence of the other subunits are not necessary for the binding function. The gamma-subunit of Fc epsilon RI is part of other receptors such as Fc gamma RIII and the T cell receptor, and therefore is likely to play an important although still undefined functional role. A detailed knowledge of how the receptor interacts with IgE and induces cellular degranulation may lead to the design of new therapeutic approaches to allergic diseases. The potential strategies are discussed.

Animals↗
PubMed1990

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.

Amino Acid Sequence↗