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M Raines

Publications and source records attributed to M Raines.

8 recordsLinked to original sources
PubMed1995

Conserved amino acids in the human granulocyte-macrophage colony-stimulating factor receptor-binding subunit essential for tyrosine phosphorylation and proliferation.

A superfamily of growth factor and cytokine receptors has recently been identified, which is characterized by four spatially conserved cysteine residues and a tryptophan-serine motif (WSXWS) in the extracellular domain and proline-rich cytoplasmic domain. The high-affinity human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, hGM-CSFR, consists of two subunits, alpha (hGM-CSFR alpha), which is required for ligand binding, and beta (hGM-CSFR beta), which is required for signal transduction. Both the alpha and beta subunits are members of the cytokine receptor superfamily. In this study, we analyzed mutations in the conserved amino acids of the alpha subunit to determine their function in signal transduction, as assayed by tyrosine phosphorylation and proliferation. Disruption of either of the conserved disulfide bonds in the extracellular domain abolishes low-affinity binding but not binding to a preformed heterodimeric complex with the beta-chain. Cells expressing receptors with mutations in cysteines 2 or 3 grew as well as cells expressing wild-type receptors in human GM-CSF (hGM-CSF) and phosphorylated the same proteins on tyrosine residues, although the level of phosphorylation may be attenuated; cysteine 3 appears to be required for generation of the true high-affinity binding site. The WSXWS motif and the cytoplasmic domain are required for function of the human GM-CSF receptor, as stable cell lines expressing receptors with these mutations were unable to proliferate continuously in hGM-CSF. Surprisingly, no function for the conserved proline-rich region of the cytoplasmic domain could be ascertained from these studies; cells expressing these receptors were indistinguishable from wild-type in both binding and functional assays.

Amino Acid Sequence↗
PubMed1995

The heavy eye phenomenon: orthoptic and ophthalmic characteristics.

A series is presented of nine patients who demonstrate the heavy eye phenomenon. Illustrations of these patients show the salient features of the phenomenon, including hypotropia, exotropia and pseudoproptosis. The condition is summarized and the pathogenesis of the eye and lid positions are discussed. The indications for surgery and some examples with results are shown. The correct diagnosis may prevent unnecessary investigation of pseudoproptosis and pseudo third-nerve palsy.

Adult↗
PubMed1994

Divergence of human alpha-chain constant region gene sequences. A novel recombinant alpha 2 gene.

IgA is the major Ig synthesized in humans and provides the first line of defense at the mucosal surfaces. The constant region of IgA heavy chain is encoded by the alpha gene on chromosome 14. Previous studies have indicated the presence of two alpha genes, alpha 1 and alpha 2, with alpha 2 existing in two allotypic forms, alpha 2 m(1) and alpha 2 m(2). Here we report the cloning and complete nucleotide sequence determination of a novel human alpha gene. Nucleotide sequence comparison with the published alpha sequences suggests that the gene arose as a consequence of recombination or gene conversion between the two alpha 2 alleles. We have expressed the gene as a chimeric protein in myeloma cells indicating that it encodes a functional protein. The novel IgA resembles IgA2 m(2) in that disulfide bonds link H and L chains. This novel recombinant gene provides insights into the mechanisms of generation of different constant regions and suggests that within human populations, multiple alleles of alpha may be present providing IgAs of different structures.

Amino Acid Sequence↗
PubMed1993

A complete description of the EGF-receptor exon structure: implication in oncogenic activation and domain evolution.

In this paper, we report that the chicken Epidermal Growth Factor Receptor (EGF-R), encoded by the proto-oncogene c-erbB, is comprised of 28 exons and spans over 75 Kb. The four previously identified domains which make up the extracellular ligand binding region of the receptor are coded for by two copies of a 300 amino acid repeat. We have demonstrated that the 3' end of each repeat coincides with the 3' end of the last exon making up the repeat. This alignment suggests that an exon-duplication may have occurred in the ligand-binding region of the gene. The transmembrane domain is encoded within a single exon and the exon boundaries of the catalytic domain closely match those defined by structural homology with other kinases. Along with the 54 chicken splice sites, the region 5' to the first exon was also sequenced. The proposed promoter region is greater than 70% GC, contains five repeats of the consensus Sp1 binding sequence and does not have a CCATT or TATA box. In addition to the presence of these characteristic housekeeping features, expression analysis confirms the promoter activity of this region and four sets of TCC repeats similar to those found in the human EGF-R promoter have been identified. To our knowledge this represents the first complete description of the exon-intron structure of the EGF-receptor family. The elucidation of the EGF-R exon structure provides insight into the domain evolution of the receptor-kinases and the mechanisms for the oncogenic conversion of EGF-R in erythroleukemias and glioblastomas.

Amino Acid Sequence↗
PubMed1991

EGF-R as a hemopoietic growth factor receptor: the c-erbB product is present in chicken erythrocytic progenitors and controls their self-renewal.

c-erbB, encoding the EGF receptor (EGF-R), was originally identified as the cellular homolog of a chicken leukemia oncogene. In humans, EGF-R is distributed widely except in hemopoietic tissues, and its amplification is associated with epidermal and glial malignancies. Here we show that c-erbB is present in normal chicken erythrocytic progenitors and transmits the mitogenic signal induced by TGF alpha. Cells that contain high affinity EGF-R are at approximately the BFU-E stage, and their long-term renewal can be induced by TGF alpha. Upon addition of insulin and erythropoietin, they can be induced to terminally differentiate into red cells. We previously demonstrated that v-erbA blocks differentiation of chicken erythrocytic progenitors but does not abrogate their growth factor dependence for proliferation. These data indicate that proliferation and differentiation are not necessarily coupled in these cells. They also demonstrate a direct role of c-erbB in the control of self-renewal of normal chicken erythrocytic progenitors and could account for the predominant leukemogenic potential of the chicken erbB gene.

Animals↗