Laminin-11.

Laminins are a family of glycoproteins which are ubiquitous components of basement membranes and play key structural and functional roles. Eleven isoforms have been identified to date; each is an alpha beta gamma heterotrimer assembled from a repertoire of five alpha, three beta and two gamma chains. Studies of laminin-11 (alpha 5 beta 2 gamma 1) illustrate the unique expression patterns and distinct functions that can be displayed by laminin isoforms. Laminin-11 is found in the glomerular basement membrane in kidney, in the neuromuscular synaptic cleft in skeletal muscle and in other tissues such as placenta and lung. Mice lacking laminin-11 exhibit defective glomerular filtration and developmental defects in neuromuscular synapse formation, with Schwann cells invading the synaptic cleft. Consistent with these observations, both motoneurons and Schwann cells distinguish laminin-11 from other isoforms in vitro. These results suggest that laminin-11 is a structural component of the basement membrane which influences cell behavior in physiologically relevant ways. A greater understanding of laminin-11 assembly and basement membrane incorporation could provide a logical basis for therapy in merosin-deficient congenital muscular dystrophy.     

Erwin Stresemann ? 22. 11. 1889?20. 11. 1972

Ohne Zusammenfassung     

Rotavirus SA11 genome segment 11 protein is a nonstructural phosphoprotein.

We investigated properties of the rotavirus genome segment 11 protein. A rotavirus SA11 genome segment 11 cDNA which contains the entire coding region was sequenced and inserted into the baculovirus transfer vector pVL941. Recombinants containing gene 11 cDNA were selected, and the gene 11 product expressed in Spodoptera frugiperda cells infected with these recombinants was inoculated into guinea pigs to produce hyperimmune antiserum. Characterization of the antiserum showed that it recognized a primary translation product with a molecular weight of 26,000 (26K protein) in recombinant-infected insect cells, in SA11-infected monkey kidney cells, and in cell-free translation reactions programmed with SA11 mRNA. A modified 28K product was also detected but only in SA11-infected monkey kidney cells. The 26K 28K proteins were shown to be phosphorylated in infected monkey kidney cells, and the 26K protein was phosphorylated in insect cells. We were unable to identify what type of modification caused the molecular weight shift to 28,000 in infected monkey kidney cells. Large amounts of the gene 11 product were detected by immunofluorescence in discrete foci in the cytoplasm of infected monkey kidney cells. Viruses of all known serotypes were also detected by immunofluorescence by using hyperimmune antiserum to the SA11 gene 11 product. The antiserum reacted with particle-depleted cytosol fractions but did not react with purified virus particles by immunoprecipitation or immunoblotting; it also did not neutralize virus infectivity in plaque reduction neutralization assays. Therefore, we conclude that the primary gene 11 product is a nonstructural phosphoprotein which we designated NS26.     

Steroids and related products. 38. 11-Aza steroids. 3. The synthesis of 11-aza 9 -steroids. I

The synthesis of 3,20-dioxygenated 11-azapregnanes, with a “normal” (a) configuration.in position 9, is described. The saturation of the 8,9-double bond of previously described unsaturated precursors can be effected not only by reduction of 9,11-iminium salts, but also catalytically, under pressure, in the presence of perchloric acid, It is shown that the 7-position of 8,9-unsaturated 11-aza steroids can be functionalized with the chromic acid-pyridine complex, the double bond of the resulting 7-ketone being prone to Birch reduction. Other, direct, pathways from saturated 11-nor 9,12-seco steroids to saturated 11-aza 9α-steroids have been explored. The crucial difficulty inherent in this approach stems from the fact that in displacement reactions involving an axial 9α-substituent, elimination competes successfully with substitution.     

Interleukin-11 and its receptor.

Interleukin (IL)-11 is a bone marrow fibroblast derived cytokine with a wide spectrum of activities in different biological systems. It has been shown that IL-11 supports the growth of certain types of plasmacytoma and hybridoma cells, enhances antigen-specific antibody responses, synergizes with IL-3 in supporting megakaryocyte colony formation, acts synergistically with IL-3 in shortening the G0 period of early progenitors, induces the synthesis of acute phase proteins, and inhibits lipoprotein lipase activity and adipocyte differentiation. The human IL-11 gene, which is localized at 19q13.3-13.4, consists of five exons and four introns. Initial biochemical characterization has identified a 151 kDa protein as the potential IL-11 binding subunit of the receptor complex. Because of the overlapping biological activities between IL-6 and IL-11, we compared the signal transduction pathways mediated by IL-6 or IL-11 in cell lines responsive to both cytokines. Results from protein tyrosine phosphorylation and immediate response gene expression suggest that there are convergent and divergent points along the signal transduction pathways utilized by IL-6 or IL-11. The IL-6 signal transducer, gp130, appears to be involved in the IL-11 mediated signaling. Other cytokines such as leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor have also been shown to utilize gp130 as a signal transducer. The significance of growth factor sharing common biological activities and signaling pathways will be discussed.