Tyrosine phosphorylation mediates ConA-induced membrane type 1-matrix metalloproteinase expression and matrix metalloproteinase-2 activation in MDA-MB-231 human breast carcinoma cells

ConA-induced cell surface activation of pro-matrix metalloproteinase-2 (pro-MMP-2) by MDA-MB-231 human breast cancer cells is apparently mediated by up-regulation of membrane type 1 MMP (MT1-MMP) through transcriptional and posttranscriptional mechanisms. Here, we have explored the respective roles of cell surface clustering and protein tyrosine phosphorylation in the ConA- induction effects. Treatment with succinyl-ConA, a variant lacking significant clusterability, partially stimulated MT1-MMP mRNA and protein levels but did not induce MMP-2 activation, suggesting that clustering contributes to the transcriptional regulation by ConA but appears to be critical for the nontranscriptional component. We further found that genistein, an inhibitor of tyrosine phosphorylation, blocked ConA-induced pro-MMP-2 activation and ConA-induced MT1-MMP mRNA level in a dose-dependent manner, implicating tyrosine phosphorylation in the transcriptional aspect. This was confirmed by the dose-dependent promotion of pro-MMP-2 activation by sodium orthovanadate in the presence of suboptimal concentrations of ConA (7.5 μg/ml), with optimal effects seen at 25 μg/g orthovanadate. Genistein did not inhibit the ConA potentiation of MMP-2 activation in MCF-7 cells, in which transfected MT1-MMP is driven by a heterologous promoter, supporting the major implication of phosphotyrosine in the transcriptional component of ConA regulation. These data describe a major signaling event upstream of MT1- MMP induction by ConA and set the stage for further analysis of the nontranscriptional component.

Crystal and molecular structure of the quinoxaline antibiotic analog TANDEM (des-N-tetramethyltriostin A)

The crystal structure of TANDEM (des-N-tetramethyltriostin A), a synthetic analogue of the quinoxaline antibiotic triostin A, has been determined independently at -135 and 7 'C and refined to R values of 0.088 and 0.147, respectively. The molecule has approximate 2-fold symmetry, with the quinoxaline chromophores and the disulfide cross-bridge projecting from opposite sides of the peptide ring. The quinoxaline groups are nearly parallel to each other and separated by about 6.5 A. The peptide backbone resembles a distorted antiparallel 13 ribbon joined by intramolecular hydrogen bonds N-H(LVal)--O(L-Ala). At low temperatures, the TANDEM molecule is surrounded by a regular first- and second-order hydration sphere containing 14 independent water molecules. At room temperature, only the first-order hydration shell is maintained. Calculations of the interplanar separation of the quinoxaline groups as a function of their orientation with respect to the peptide ring support the viability of TANDEM to intercalate bifunctionally into DNA.

Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3-14

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is an autosomal dominantly inherited form of primary hyperparathyroidism. Although comprising only about 1% of cases of primary hyperparathyroidism, identification and functional analysis of a causative gene for FIHP is likely to advance our understanding of parathyroid physiology and pathophysiology. METHODS: A genome-wide screen of DNA from seven pedigrees with FIHP was undertaken in order to identify a region of genetic linkage with the disorder. RESULTS: Multipoint linkage analysis identified a region of suggestive linkage (LOD score 2.68) on chromosome 2. Fine mapping with the addition of three other families revealed significant linkage adjacent to D2S2368 (maximum multipoint LOD score 3.43). Recombination events defined a 1.7 Mb region of linkage between D2S2368 and D2S358 in nine pedigrees. Sequencing of the two most likely candidate genes in this region, however, did not identify a gene for FIHP. CONCLUSIONS: We conclude that a causative gene for FIHP lies within this interval on chromosome 2. This is a major step towards eventual precise identification of a gene for FIHP, likely to be a key component in the genetic regulation of calcium homeostasis.

Kukuruza Raĭony vozdelyvanii︠a︡ kukuruzy : nailuchshie sorta i sredni︠a︡i︠a︡ urozhaĭnost' sukhogo zerna na 1 des. po dannym seti opytnykh uchastkov iuga Rossii i postoi︠a︡nnykh opytnykh uchrezhdenniĭ

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Rückläufige Tendenz des Dorschbestandes in der zentralen Ostsee hält an - (262. Forschungsreise des FFK "Solea" vom 31.1.-10.2.1989)

Die stark rückläufige Tendenz des Dorschbestandes in der zentralen Ostsee, östlich von Bornholm, über die in den letzten Jahren berichtet wurde, hält nach den Untersuchungen des FFK "Solea" (31.1. - 10.2.1989)an. Im Bornholm Becken lag der durchschnittliche Grundschleppnetzfang je Stunde auf Wassertiefen flacher als 75 m, wo ausreichende Sauerstoffverhältnisse am Boden waren, im EG-Bereich mit 2,5 Korb nochmals niedriger als 1988 (3 Korb). Er lag damit fast um 2/3 niedriger als im langjährigen Mittel 1980-1986. Die besten Fänge wurden mit jeweils 3,5 Korb im Ostzipfel des EG-Meeres, im sogenannten "Bermuda Dreieck", und südlich von Nexö auf jeweils 72 m Wassertiefe erzielt. Im großen und ganzen war der Dorsch im Wassertiefenbereich zwischen 50 und 75 m des Bornholm Beckens recht gleichmäßig verteilt.

Recherches sur le développement des organes genitaux de quelques Gasteropodes hermaphrodites. 1. Thèse ; Propositions données par la Faculté. 2e. Thèse

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Campagnes Nizery: Togo 1 (26 et 27/01/83) et Togo 2 (07 au 10/06/83). Resultats des chalutages

This publication gives the results of the bottom trawlings made during the cruises Togo 1 and Togo 2 by the oceanographic research vessel "Andre Nizery" on the continental shelf of Togo during the estimation program of halieutic resources. The report includes: 1 - The report of the cruises Togo 1 and Togo 2; 2 - Some information on the presentation of the results; 3 - The trawl recording cards for the 2 cruises; 4 - The length frequency distributions of the measured samples.