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Biomedical subjects

K Damm

Publications and source records attributed to K Damm.

26 records · Page 2Linked to original sources
PubMed1989

Molecular cloning of the chicken myelomonocytic growth factor (cMGF) reveals relationship to interleukin 6 and granulocyte colony stimulating factor.

Normal as well as retrovirally transformed avian myeloid precursor cells require the colony stimulating factor cMGF for their survival, proliferation and colony formation in vitro. cMGF has been shown to be a glycoprotein which is active in the picomolar concentration range. Co-expression of kinase type oncogenes in v-myb or v-myc transformed myeloid cells induces cMGF expression and confers factor independence via an autocrine mechanism. Here we describe the molecular cloning of cMGF from a myeloblast cDNA library and show that it is a 201 amino acid residue secretory protein which is modified by signal peptide cleavage and glycosylation during translocation into the lumen of membrane vesicles. A bacterially expressed trpE-cMGF fusion protein induces proliferation of E26 transformed myeloblasts in a cMGF bioassay suggesting that glycosylation is not absolutely necessary for biological activity. Sequence comparison reveals that cMGF is distantly related to G-CSF and IL-6.

Amino Acid Sequence↗
PubMed1987

A single point mutation in erbA restores the erythroid transforming potential of a mutant avian erythroblastosis virus (AEV) defective in both erbA and erbB oncogenes.

We have characterized the v-erbA and v-erbB oncogenes of td359, a transformation-defective mutant of avian erythroblastosis virus (AEV) unable to transform erythroblasts, and the revertant r12, obtained after in vivo passage of the mutant. Molecular cloning, sequencing, construction of chimeric viruses and testing of their oncogenic capacities revealed that both oncogenes of td359 are mutated and biologically defective. The r12 virus, although still containing a mutant v-erbB gene, recovered its erythroid transforming potential by acquiring a highly active gag-erbA gene. These results demonstrate that two co-operating oncogenes, an active v-erbA and a defective v-erbB, can transform a cell type not transformed by either oncogene alone. Furthermore, a single amino acid substitution inactivated the td359 v-erbA protein and we show that its reversion led to the reactivation of the protein. This lesion is located in the same region as several previously described inactivating mutations of glucocorticoid receptors, suggesting that the structure/function relationship of the virally transduced form of the c-erbA/thyroid hormone receptor is closely similar to that of steroid hormone receptors.

Alpharetrovirus↗
PubMedDate not supplied

Functional properties of deoxycorticosterone and spironolactone: molecular characterization and effects on sleep-endocrine activity.

Adrenal steroid hormones are capable of interfering with a variety of behavioral phenomena including sleep. The mechanisms appear to involve effects at the cell membrane as well as nuclear actions mediated by intracellular mineralo- and glucocorticosteroid receptors (MR and GR). We employed the MR agonist deoxycorticosterone (DOC) and the MR antagonist spironolactone (SP) to study the role of MRs in the regulation of human sleep. We also tested whether the effects of DOC upon the sleep EEG and nocturnal hormone secretion (growth hormone and cortisol) are compatible with those predicted for its major metabolite tetrahydro-DOC (THDOC): electrophysiological and animal experiments had suggested that THDOC would act as a hypnotic via positive modulation of the GABAA receptor. Because neither DOC nor SP affected the sleep EEG substantially, the involvement of MRs in the regulation of sleep needs further study. The sleep-endocrine data showed a suppressive effect of DOC upon plasma cortisol concentrations and an earlier occurrence of nocturnal GH maxima, which can be plausibly explained by GR or sigma receptor-mediated effects. Molecular characterization of DOC and SP confirmed a relatively strong effect of DOC upon transactivation via MR and no effect of SP on the GR-mediated transcription rate. In addition, the possibility that a low dose of the mineralocorticoid DOC may serve as a prodrug for the potential hypnotic THDOC is not supported by the current data.

Adult↗
PubMedDate not supplied

The c-erb-A protein is a high-affinity receptor for thyroid hormone.

Hormone binding and localization of the c-erb-A protein suggest that it is a receptor for thyroid hormone, a nuclear protein that binds to DNA and activates transcription. In contrast, the product of the viral oncogene v-erb-A is defective in binding the hormone but is still located in the nucleus.

Amino Acid Sequence↗