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Mammalian Members (mammalian + member)
Selected AbstractsMorphogens and cell survival during developmentDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2005Patrick Mehlen Abstract The notion of "morphogens" is an important one in developmental biology. By definition, a morphogen is a molecule that emanates from a specific set of cells that is present in a concentration gradient and that specifies the fate of each cell along this gradient. The strongest candidate morphogens are members of the transforming growth factor-, (TGF-,), Hedgehog (Hh), and Wnt families. While these morphogens have been extensively described as differentiation inducers, some reports also suggest their possible involvement in cell death and cell survival. It is frequently speculated that the cell death induction that is found associated with experimental removal of morphogens is the manifestation of abnormal differentiation signals. However, several recent reports have raised controversy about this death by default, suggesting that cell death regulation is an active process for shaping tissues and organs. In this review, we will present morphogens, with a specific emphasis on Sonic Hedgehog, a mammalian member of the Hh family, not as a positive regulators of cell differentiation but as key regulators of cell survival. © 2005 Wiley Periodicals, Inc. J Neurobiol 64: 357,366, 2005 [source] Hsp105, upregulates hsp70 gene expression through signal transducer and activator of transcription-3FEBS JOURNAL, Issue 20 2009Nobuyuki Yamagishi Hsp105, and Hsp105, are mammalian members of the Hsp105/110 family, a divergent subgroup of the Hsp70 family. Hsp105, is expressed constitutively and induced by various forms of stress, whereas Hsp105, is an alternatively spliced form of Hsp105, that is expressed specifically during mild heat shock. In a report, it was shown that Hsp105, and Hsp105, localize to the cytoplasm and of nucleus of cells, respectively, and that Hsp105,, but not Hsp105,, induces the expression of Hsp70 in mammalian cells. Here, we examined the mechanism by which Hsp105, induces the expression of Hsp70. Using a series of deletion mutants of Hsp105,, it was revealed that the region between amino acids 642 and 662 of Hsp105, is necessary for the activation of the hsp70 promoter by Hsp105,. Furthermore, it was shown that signal transducer and activator of transcription (STAT)-3 bound to the sequence of the hsp70 promoter between ,206 and ,187 bp, and that mutations of this sequence abrogated the activation of the hsp70 promoter by Hsp105,. In addition, overexpression of Hsp105, stimulated the phosphorylation of STAT3 at Tyr705 and its translocation to the nucleus. Downregulation of STAT3 expression resulted in reduction of the activation of the hsp70 promoter by Hsp105,. Furthermore, downregulation of Hsp105, reduced the expression of Hsp70 in heat-shocked cells. On the basis of these findings, it is suggested that Hsp105, induces Hsp70 expression markedly through the STAT3 pathway in heat-shocked cells. This may represent the mechanism that connects the heat shock protein and STAT families for cell defense against deleterious stress. [source] Regulation of phosphoinositide signaling by the inositol polyphosphate 5-phosphatasesIUBMB LIFE, Issue 8 2006Megan V. Astle Abstract Phosphoinositide signaling molecules control cellular growth, proliferation and differentiation, intracellular vesicle trafficking, and cytoskeletal rearrangement. The inositol polyphosphate 5-phosphatase family remove the D-5 position phosphate from PtdIns(3,4,5)P3, PtdIns(4,5)P2 and PtdIns(3,5)P2 forming PtdIns(3,4)P2, PtdIns(4)P and PtdIns(3)P respectively. This enzyme family, comprising ten mammalian members, exhibit seemingly non-redundant functions including the regulation of synaptic vesicle recycling, hematopoietic cell function and insulin signaling. Here we highlight recently established insights into the functions of two well characterized 5-phosphatases OCRL and SHIP2, which have been the subject of extensive functional studies, and the characterization of recently identified members, SKIP and PIPP, in order to highlight the diverse and complex functions of this enzyme family. iubmb Life, 58: 451 - 456, 2006 [source] Development and Biological Evaluation of a Novel Aurora A Kinase InhibitorCHEMBIOCHEM, Issue 3 2009Teresa Sardon Dr. Abstract Stop dividing: In the quest for antitumorigenic compounds, aurora A kinase has recently emerged as a potential drug target. In this paper three novel aurora inhibitors (shown in the illustration) have been tested for their biological activity in cultured cells. One of them (TC-28) appears to be a promising specific aurora A inhibitor in vivo. The aurora kinase family groups several serine/threonine kinases with key regulatory functions during cell division. The three mammalian members, aurora A, B and C, are frequently over-expressed in human tumors and the aurora A gene is located in a genomic region frequently amplified in breast and colon cancer. All these data have fuelled the idea that aurora kinases are promising targets for anticancer therapy. Indeed some inhibitory compounds are currently being evaluated in clinical trials. However, it was recently shown that mutations in the targeted kinase can confer resistance to a broad range of inhibitors and render patients resistant to treatments. Moreover, aurora A over-expression results in increased resistance to antimitotic agents. The development of new compounds targeting aurora A is therefore highly relevant. We describe here the synthesis of three novel aurora kinase inhibitors, TC-28, TC-34 and TC-107. We report their properties as aurora inhibitors in vitro and their effect on human tissue culture cell lines. Interestingly, our results show that TC-28 has properties compatible with the specific inhibition of aurora A, in vivo. [source] | |||||||||||||