Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity

jerry submitted, created time 5 months 3 weeks (www.cancercell.org)

Expression of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase associated with cell proliferation and survival, is overactive in many tumors of epithelial origin. Blockade of the kinase activity of EGFR has been used for cancer therapy; however, by itself, it does not seem to reach maximum therapeutic efficacy. We report here that in human cancer cells, the function of kinase-independent EGFR is to prevent autophagic cell death by maintaining intracellular glucose level through interaction and stabilization of the sodium/glucose cotransporter 1 (SGLT1).

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Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy

bianjie submitted, created time 1 year 1 month (www.pnas.org)

Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit.

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Modelling of the ABL and ARG proteins predicts two functionally critical regions that are natively unfolded.

A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity

angelfish submitted, created time 1 year 5 months (www.jem.org)

"IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines

Submit comment | Blog It | Email It | Keywords: receptor tyrosine kinase (RTK) cyclin dependent kinase 1 (Cdk1) protein kinase B tyrosine kinase

Structural Basis for the Inhibition of Tyrosine Kinase Activity of ZAP-70

alpha submitted, created time 1 year 5 months (www.cell.com)

"ZAP-70, a cytoplasmic tyrosine kinase required for T cell antigen receptor signaling, is controlled by a regulatory segment that includes a tandem SH2 unit responsible for binding to immunoreceptor tyrosine-based activation motifs (ITAMs). The crystal structure of autoinhibited ZAP-70 reveals that the inactive kinase domain adopts a conformation similar to that of cyclin-dependent kinases and Src kinases. The autoinhibitory mechanism of ZAP-70 is, however, distinct and involves interactions between the regulatory segment and the hinge region of the kinase domain that reduce its flexibility

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Bidirectional Eph–ephrin signaling during axon guidance

amanda submitted, created time 1 year 6 months (www.sciencedirect.com)

"Ephrins are cell-surface tethered guidance cues that bind to Eph receptor tyrosine kinases in trans on opposing cells. In the developing nervous system, the Eph–ephrin signaling system controls a large variety of cellular responses including contact-mediated attraction or repulsion, adhesion or de-adhesion, and migration. Eph–ephrin signaling can be bidirectional, and is subject to modulation by ectodomain cleavage of ephrins and by Eph–ephrin endocytosis

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Differential Activation of Insulin Receptor Substrates 1 and 2 by Insulin-Like Growth Factor-Activated Insulin Receptors

badboy submitted, created time 1 year 6 months (mcb.asm.org)

"The specific activation of IRS-2 by IGF-I through the IR does not result in activation of the extracellular signal-regulated kinase pathway but does induce delayed low-level activation of the phosphatidylinositol 3-kinase pathway and biological effects such as enhanced cell viability and protection from apoptosis. These findings suggest that IGF-I can function directly through the IR and that the observed effects of IGF-I on insulin sensitivity may be the result of direct facilitation of insulin action by IGF-I costimulation of the IR in insulin target tissues. "

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