Inhibition of the p110α isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis
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چکیده
منابع مشابه
Inhibition of the p110α isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis
Understanding the direct, tumor cell-intrinsic effects of PI 3-kinase (PI3K) has been a key focus of research to date. Here, we report that cancer cell-extrinsic PI3K activity, mediated by the p110α isoform of PI3K, contributes in an unexpected way to tumor angiogenesis. In syngeneic mouse models, inactivation of stromal p110α led to increased vascular density, reduced vessel size, and altered ...
متن کاملOncogenic Mutations of p110α Isoform of PI 3-Kinase Upregulate Its Protein Kinase Activity
In addition to lipid kinase activity, the class-I PI 3-kinases also function as protein kinases targeting regulatory autophosphorylation sites and exogenous substrates. The latter include a recently identified regulatory phosphorylation of the GM-CSF/IL-3 βc receptor contributing to survival of acute myeloid leukaemia cells. Previous studies suggested differences in the protein kinase activity ...
متن کاملClass IA Phosphatidylinositol 3-Kinase Isoform p110α Mediates Vascular Remodeling.
OBJECTIVE Neointima formation after vascular injury remains a significant problem in clinical cardiology, and current preventive strategies are suboptimal. Phosphatidylinositol 3'-kinase is a central downstream mediator of growth factor signaling, but the role of phosphatidylinositol 3'-kinase isoforms in vascular remodeling remains elusive. We sought to systematically characterize the precise ...
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The combination of molecular modeling and X-ray crystallography has failed to yield a consensus model of the mechanism for selective binding of inhibitors to the phosphoinositide 3-kinase (PI3K) p110 α-isoform. Here we have used kinetic analysis to determine that the p110α-selective inhibitor 2-methyl-5-nitro-2-[(6-bromoimidazo[1,2-α]pyridin-3-yl)methylene]-1-methylhydrazide-benzenesulfonic aci...
متن کاملThe p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN.
Inactivation of PI 3-kinase (PI3K) signalling is critical for tumour suppression by PTEN. This is thought to be a unidirectional relationship in which PTEN degrades the lipids produced by PI3K, thus controlling cell proliferation, survival and migration. We now show that this relationship is in fact bidirectional, whereby PI3K reciprocally controls PTEN. We report that the p110delta PI3K negati...
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ژورنال
عنوان ژورنال: The Journal of Cell Biology
سال: 2013
ISSN: 0021-9525,1540-8140
DOI: 10.1083/jcb.2027oia99