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Biomedical subjects

M Theelen

Publications and source records attributed to M Theelen.

6 recordsLinked to original sources
PubMed1999

Protein kinase Czeta is a negative regulator of protein kinase B activity.

Protein kinase B (PKB), also known as Akt or RAC-PK, is a serine/threonine kinase that can be activated by growth factors via phosphatidylinositol 3-kinase. In this article we show that PKCzeta but not PKCalpha and PKCdelta can co-immunoprecipitate PKB from CHO cell lysates. Association of PKB with PKCzeta was also found in COS-1 cells transiently expressing PKB and PKCzeta, and moreover we found that this association is mediated by the AH domain of PKB. Stimulation of COS-1 cells with platelet-derived growth factor (PDGF) resulted in a decrease in the PKB-PKCzeta interaction. The use of kinase-inactive mutants of both kinases revealed that dissociation of the complex depends upon PKB activity. Analysis of the activities of the interacting kinases showed that PDGF-induced activation of PKCzeta was not affected by co-expression of PKB. However, both PDGF- and p110-CAAX-induced activation of PKB were significantly abolished in cells co-expressing PKCzeta. In contrast, co-expression of a kinase-dead PKCzeta mutant showed an increased induction of PKB activity upon PDGF treatment. Downstream signaling of PKB, such as the inhibition of glycogen synthase kinase-3, was also reduced by co-expression of PKCzeta. A clear inhibitory effect of PKCzeta was found on the constitutively active double PKB mutant (T308D/S473D). In summary, our results demonstrate that PKB interacts with PKCzeta in vivo and that PKCzeta acts as a negative regulator of PKB.

Amino Acid Sequence↗
PubMed1990

Proliferation "hot spots" in adult avian ventricular zone reveal radial cell division.

Neurogenesis in the adult avian brain is restricted to the telencephalon. New neurons originate in the ventricular zone (VZ) from cells that have not been identified. We mapped the position of [3H]thymidine-labeled cells in the walls of the ventricles of the adult canary brain. Labeled VZ cells were restricted to the telencephalon (lateral ventricles) and concentrated in "hot spots". The coincidence of these hot spots with regions rich in radial cells suggested that radial cells may be the cells undergoing mitosis. We used smears prepared from fragments of the VZ containing the hot spots to show directly that radial cells accumulate [3H]thymidine. In addition, grain counts at different survival times demonstrated that these cells divide. Hot spots of VZ cell division also coincided with sites of neuronal origin. We suggest that radial cell division may give rise to new neurons.

Animals↗
PubMed1988

Birth of projection neurons in the higher vocal center of the canary forebrain before, during, and after song learning.

The higher vocal center (HVc) of the canary brain projects to two forebrain nuclei: robustus archistriatalis (RA) and area X of lobus parolfactorius. The time of birth of HVc neurons projecting to these two regions was determined by combining [3H]thymidine autoradiography and retrograde fluorogold uptake. Birds were sacrificed at 13 months of age, 4 days after fluorogold injections into area X or RA. A single injection of [3H]thymidine in ovo (embryonic day 9) labeled 76% of area X-projecting cells and 0.8% of cells projecting to RA. The great majority of RA-projecting cells were produced during posthatching development (posthatching day 10-240; P10-P240), with a peak at P60 and a hiatus at P120. HVc reaches full adult size by P240, yet at that age the production of new RA-projecting cells continued at a rate comparable to that recorded during posthatching development. Late production of neurons interconnecting two distant regions of the brain may regulate source to target cell population size. Male canaries start to sing at P40. During subsequent months, they imitate external models and their song becomes more structured and stereotyped. At sexual maturity (P240), song is stable. Three interpretations are offered: (i) neurogenesis of RA-projecting cells is related to learning, and learning continues even after achievement of pattern stability; (ii) neurogenesis of RA-projecting cells is not related to learning; (iii) the production of RA-projecting cells serves different purposes during development and after sexual maturity.

Aging↗
PubMed1988

Mapping of radial glia and of a new cell type in adult canary brain.

Frontal and coronal sections of adult male and female canary brain were stained with a monoclonal antibody to vimentin using an immunoperoxidase technique; some sections were counterstained with cresyl violet. The position of radial glia cells was mapped using a computer-linked microscope. The telencephalon was found to have a rich set of radial glia. The long processes of these radial glia showed a mediolateral orientation, and were much more abundant in some parts of the telencephalon (e.g., hyperstriatum, caudal neostriatum, and lobus parolfactorius) than in others (e.g., anterior neostriatum, archistriatum, and septum), which had few or no radial glia fibers. A small, elongated cell type not previously described in adult avian brain was frequently seen to be associated with the long processes of the radial glia, oriented in the same direction and often in close apposition. The position of these cells was also systematically mapped, and they were found to be virtually absent outside of the telencephalon. The relation between radial glia fibers and the small, elongated cells was most commonly seen close to the lateral ventricle of the forebrain, where the radial glia cells have their cell bodies. The above observations suggest that there may be a functional relation between radial glia and the small, elongated cells. We hypothesize that the latter cells are young migrating neurons. This hypothesis is tested in a separate publication (A. Alvarez-Buylla and F. Nottebohm, unpublished observations).

Animals↗
PubMed1985

Isolation, purification, and characterization of a mouse plasmacytoma cell surface glycoprotein involved in the resistance of the tumor cells to immune destruction.

Cells of a subline of the mouse plasmacytoma LPC-1 are resistant to lysis by cytotoxic T-lymphocytes, probably as a result of the blocking of the major histocompatibility gene complex-encoded cell surface antigens by a trypsin-sensitive glycoprotein of approximately 160 kilodaltons. This glycoprotein (gp 160) was extracted from LPC-1 cells with 1.5 M urea and was further purified by ammonium sulfate precipitation and Sephacryl S-300 gel filtration. The gp 160 consists of a single peptide chain rich in sialic acid residues (10% of total molecular weight) and has an acidic isoelectric point. The amino acid composition of gp 160 is compatible with the linkage of carbohydrates (galactose, glucosamine, and sialic acid) to the protein portion. The apparent weak attachment of gp 160 to the cell membrane could explain the finding that LPC-1 cells easily revert from the resistant to the sensitive to the immune lysis phenotype.

Amino Acids↗