Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases.

The critical pathways through which protein-tyrosine kinases induce cellular proliferation and malignant transformation are not well defined. As microinjection of antibodies against p21ras can block the biological effects of both normal and oncogenic tyrosine kinases, it is likely that they require functional p21ras to transmit their mitogenic signals. No biochemical link has been established, however, between tyrosine kinases and p21ras. We have identified a non-catalytic domain of cytoplasmic tyrosine kinases, SH2, that regulates the activity and specificity of the kinase domain. The presence of two adjacent SH2 domains in the p21ras GTPase-activating protein (GAP) indicates that GAP might interact directly with tyrosine kinases. Here we show that GAP, and two co-precipitating proteins of relative molecular masses 62,000 and 190,000 (p62 and p190) are phosphorylated on tyrosine in cells that have been transformed by cytoplasmic and receptor-like tyrosine kinases. The phosphorylation of these polypeptides correlates with transformation in cells expressing inducible forms of the v-src or v-fps encoded tyrosine kinases. Furthermore, GAP, p62 and p190 are also rapidly phosphorylated on tyrosine in fibroblasts stimulated with epidermal growth factor. Our results suggest a mechanism by which tyrosine kinases might modify p21ras function, and implicate GAP and its associated proteins as targets of both oncoproteins and normal growth factor receptors with tyrosine kinase activity. These data support the idea that SH2 sequences direct the interactions of cytoplasmic proteins involved in signal transduction.     

用模糊综合评判法评价变电所所址

变电所选址是电力系统规划的一个重要环节。但与变电所所址有关的因素错综复杂,很难仅凭经验就能确定最佳所址。本文采用模糊综合评判方法对备选所址进行评判,确定其优先次序。在模糊综合评判中,各因素的权重分配对结果起决定性作用,用层次分析法确定与所址密切相关的各个因素相对总体目标而言的权重,使得权重的确定更科学。算例表明该方法是可行的。     

Caenorhabditis elegans gene ced-9 protects cells from programmed cell death.

The gene ced-9 of the nematode Caenorhabditis elegans acts to protect cells from programmed cell death. A mutation that abnormally activates ced-9 prevents the cell deaths that occur during normal C. elegans development. Conversely, mutations that inactivate ced-9 cause cells that normally live to undergo programmed cell death; these mutations result in embryonic lethality, indicating that ced-9 function is essential for development. The ced-9 gene functions by negatively regulating the activities of other genes that are required for the process of programmed cell death.     

Space geodetic evidence for rapid strain rates in the New Madrid seismic zone of central USA

In the winter of 1811-1812, near the town of New Madrid in the central United States and more than 2,000 km from the nearest plate boundary, three earthquakes within three months shook the entire eastern half of the country and liquefied the ground over distances far greater than any historic earthquake in North America. The origin and modern significance of these earthquakes, however, is highly contentious. Geological evidence demonstrates that liquefaction due to strong ground shaking, similar in scale to that generated by the New Madrid earthquakes, has occurred at least three and possibly four times in the past 2,000 years (refs 4-6), consistent with recurrence statistics derived from regional seismicity. Here we show direct evidence for rapid strain rates in the area determined from a continuously operated global positioning system (GPS) network. Rates of strain are of the order of 10(-7) per year, comparable in magnitude to those across active plate boundaries, and are consistent with known active faults within the region. These results have significant implications for the definition of seismic hazard and for processes that drive intraplate seismicity.