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101.
BPGAP1 interacts with cortactin and facilitates its translocation to cell periphery for enhanced cell migration
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Rho GTPases control cell dynamics during growth and development. They are activated by guanine nucleotide exchange factors and inactivated by GTPase-activating proteins (GAPs). Many GAPs exist with various protein modules, the functions of which largely remain unknown. We recently cloned and identified BPGAP1 as a novel RhoGAP that coordinately regulates pseudopodia and cell migration via the interplay of its BNIP-2 and Cdc42GAP homology, RhoGAP, and the proline-rich domains. To further elucidate the molecular mechanism underlying cell dynamics control by BPGAP1, we used protein precipitations and matrix-assisted laser desorption/ionization mass spectrometry and identified cortactin, a cortical actin binding protein as a novel partner of BPGAP1 both in vitro and in vivo. Progressive deletion studies confirmed that cortactin interacted directly and constitutively with the proline-rich motif 182-PPPRPPLP-189 of BPGAP1 via its Src homology 3 domain. Together, they colocalized to periphery and enhanced cell migration. Furthermore, substitution of prolines at 184 and 186 with alanines abolished their interaction. Consequently, this BPGAP1 mutant failed to facilitate translocation of cortactin to the periphery, and no enhanced cell migration was observed. These results provide the first evidence that a RhoGAP functionally interacts with cortactin and represents a novel determinant in the regulation of cell dynamics. 相似文献
102.
Molecular classification of cancer types from microarray data using the combination of genetic algorithms and support vector machines 总被引:11,自引:0,他引:11
Simultaneous multiclass classification of tumor types is essential for future clinical implementations of microarray-based cancer diagnosis. In this study, we have combined genetic algorithms (GAs) and all paired support vector machines (SVMs) for multiclass cancer identification. The predictive features have been selected through iterative SVMs/GAs, and recursive feature elimination post-processing steps, leading to a very compact cancer-related predictive gene set. Leave-one-out cross-validations yielded accuracies of 87.93% for the eight-class and 85.19% for the fourteen-class cancer classifications, outperforming the results derived from previously published methods. 相似文献
103.
Four species of Adlerius phlebotomine sandflies have been recorded in China, namely: P. chinensis Newstead, 1916 (Pc), P. fengi Leng & Zhang, 1994; P. longiductus Parrot, 1928 and P. sichuanensis Leng & Yin, 1983 (Ps). Adlerius phlebotomies are the main vectors of visceral leishmaniasis (VL) in China; three of them are acknowledged as VL vectors and P. fengi is considered a potential VL vector for southwestern mountainous region. Different opinion has been raised to the validity of identity of Ps by some investigators from Shanghai and Shanxi who consider Ps to be a large type of Pc instead of an isolate species. The center of controversy is whether Ps is an isolate taxon or a large type of Pc. The present authors have carried out a series of comparative studies for these two flies on: 1 quantitative and qualitative morphological characters of four Chinese Adlerius phlebotomies; and 2. differences in geographical distribution. All specimens of Pc and Ps used in the present study are collected where their holotypes-paratypes were produced--West Mountain, West Suburb, Beijing and Lixian County, Sichuan Province. The results have forcefully proved that Ps is an isolate species instead of a so-called large type Pc according to the concept of species. The clarification of their taxonomical identities is meaningful because both of them are VL vectors in different epidemic areas in China; especially Ps is an important VL vector in high mountainous regions of southwestern China and some extend to the Loess Plateau of northwestern China, where VL still exists and it is also the first Phlebotomine sandfly discovered in Tibet, the locality being near Assam in India (Leng et al. 1990). 相似文献
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106.
Chronic immune activation is associated with impaired signal transduction. Since such activation is commonly found during HIV-1 infection, we studied cellular responses to non-specific T-cell receptor stimulation of PBMC obtained from 20 HIV-1 non-infected individuals and 23 highly or partially immune activated HIV-1 infected individuals. PBMC proliferation and ERK-1/2 phosphorylation following anti-CD3 stimulation, and constitutive levels of Cbl-b, were determined. Increased levels of Cbl-b, decreased proliferation, and lower ERK-1/2 phosphorylation were found in PBMC of highly immune activated HIV-1 infected individuals. The elevated expression of Cbl-b and impaired phosphorylation of ERK-1/2 associated with immune activation probably contribute to the attenuated proliferative and cellular responses characteristic of HIV-1 infection. Therefore, targeting immune negative modulators, such as Cbl-b, may serve as a novel approach for controlling HIV-1 disease progression. 相似文献
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108.
Rad6p plays important roles in post-replication DNA repair, chromatin organization, gene silencing and meiosis. In this study, we show that Rad6p also regulates yeast-hypha morphogenesis in the human pathogen Candida albicans. CaRAD6 gene and cDNAs were isolated and characterized revealing that the gene carries two 5'-proximal introns. CaRad6p shows a high degree of sequence similarity to Rad6 proteins from fungi to man (60-83% identity), and it suppresses the UV sensitivity and lack of induced mutagenesis displayed by a Saccharomyces cerevisiae rad6 mutant. In C. albicans, CaRAD6 expression is induced in response to UV, and CaRad6p depletion confers UV sensitivity, confirming that Rad6p serves a role in protecting this fungus against UV damage. CaRAD6 overexpression inhibits hyphal development, whereas CaRad6p depletion enhances hyphal growth. Also, CaRAD6 mRNA levels decrease during the yeast-hypha transition. These effects are dependent on Efg1p, but not Cph1p, indicating that CaRad6p acts specifically through the Efg1p morphogenetic signalling pathway to repress yeast-hypha morphogenesis. 相似文献
109.
Increased guard cell cytosolic [Ca2+] is known to be involved in signal transduction pathways leading to stomatal closure, and inhibit the inward rectifying guard cell K+ channel KAT1. Guard cell calcium-dependent protein kinase (CDPK) has been shown to phosphorylate KAT1; such phosphorylation is known to modulate other K+ channels involved in signal transduction cascades. The work reported here focused on demonstrating CDPK-dependent inhibition of KAT1 currents. A cDNA encoding soybean CDPK was generated and it's translation product was shown to be functional; demonstrating Ca2+-dependent autophosphorylation and phosphorylation of a target protein. Ion currents were monitored using voltage clamp techniques upon expression of KAT1 in Xenopus laevis oocytes. Coexpression of recombinant CDPK with KAT1 in oocytes altered the kinetics and magnitude of induced K+ currents; at a given hyperpolarizing command voltage, the magnitude of KAT1 currents was reduced and the half-time for channel activation was increased. This finding supports a model of Ca2+-dependent ABA inhibition of inward K+ currents in guard cells as being mediated by CDPK phosphorylation of KAT1. 相似文献
110.
Junhong Leng Ping Shao Cuiping Zhang Huiguang Tian Fuxia Zhang Shuang Zhang Ling Dong Lili Li Zhijie Yu Juliana C. N. Chan Gang Hu Xilin Yang 《PloS one》2015,10(3)