Disease relevance of PIK3R1

• Escherichia coli expressed soybean PI3K phosphorylated phosphatidylinositol specifically at the D-3 position of the inositol ring to generate phosphatidylinositol 3-phosphate [1].
• In BAEC, activation of eNOS by LPA is completely blocked by pertussis toxin, by the intracellular calcium chelator BAPTA (1,2-bis(aminophenoxy) ethane-N,N,N',N'-tetraacetic acid), and by the phosphoinositide 3-kinase (PI3-K) inhibitor wortmannin, but is unaffected by U0126, an inhibitor of mitogen-activated protein (MAP) kinase pathways [2].
• However, activation of PI3K was not required for activation of ERK1/2, implying a parallel involvement of these pathways in the proliferative response of fibroblasts to hypoxia [3].
• The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is involved in various malignancies, but the role of PI3-K/Akt pathway in Epstein-Barr virus (EBV) infected Burkitt's lymphoma (BL) cells remains unclear [4].

High impact information on PIK3R1

• Vps34p shares significant sequence similarity with the catalytic subunit of bovine phosphatidylinositol (PI) 3-kinase [the 110-kilodalton (p110) subunit of PI 3-kinase], which is known to interact with activated cell surface receptor tyrosine kinases [5].
• The angiogenic program is regulated by extracellular factors, whose input is integrated at least in part at the level of signal transduction pathways driven by phosphoinositide 3 kinase (PI3K) and phospholipase Cgamma (PLCgamma) [6].
• The underlying mechanism by which PLCgamma antagonized tube formation appeared to be by competing with PI3K for their common substrate, phosphatidylinositol-4,5-bisphosphate [6].
• The RAS-independent activation of MAP kinase by LPA was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) or by overexpression of a dominant-negative mutant of the gamma isoform of PI3K [7].
• We report the cloning and characterization of soybean PI3K cDNAs and present evidence for the induction of a distinctive form of this enzyme specific to nodule organogenesis [1].

Chemical compound and disease context of PIK3R1

• Because lysophosphatidic acid (LPA) has been proposed to be responsible for this activity of PCM and is known to activate the G(i) protein, inhibitors of the G protein pertussis toxin and of the associated phosphatidylinositol 3-kinase (PI3K) wortmannin were used [8].

Biological context of PIK3R1

• Inhibitors of PPARalpha, PI3 kinase and MAPK, respectively, markedly attenuate bezafibrate-induced upregulation of eNOS [9].
• Thus, with impaired PI 3-kinase signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration [10].
• The interactions of the N-terminal src homology (SH2) domain (N-SH2) of the 85 kDa subunit of phosphatidylinositol 3'-kinase (PI-3K) with phosphotyrosine (ptyr) and a series of ptyr-containing peptides have been examined by NMR spectroscopy [11].
• Shear stress increased Cbl phosphorylation to 2.9-fold of control and Cbl association with the regulatory PI-3 kinase subunit p85 to 5.4-fold [12].
• Pretreatment with either the MEK1 inhibitor U0126 or PI3-kinase inhibitor LY294002 sensitized BAE cells to TNF-induced apoptosis [13].

Anatomical context of PIK3R1

• Fluid shear stress can activate PI-3 kinase and JNK in vascular endothelial cells [12].
• Our results suggest that Cbl plays a critical role in the shear stress induction of PI 3-kinase and JNK activities, and that this shear-induced activation requires the interaction of endothelial integrins with extracellular matrix proteins [12].
• By using both pharmacologic and genetic approaches, we found that in addition to ERK1/2, phosphatidylinositol 3-kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and p70 S6K-dependent signaling pathways are required for ATP-induced proliferation of adventitial fibroblasts [14].
• RESULTS: PI-3K activity was found in both lens epithelial cells and fiber cells [15].
• Here, we show that infected B lymphocytes display constitutive phosphoinositide 3-kinase (PI3-K) activity, which appears to be necessary for proliferation, but not survival [16].

Associations of PIK3R1 with chemical compounds

• In order to establish which of the IGF-I signaling pathways contributed to anti-TGF-beta(1) and anti-apoptotic effects, the inhibitors of PI3-kinase - (LY 294002) and MEK- (MAPKK for ERK) (PD 098059) mediated signaling pathways were applied to our model [17].
• ERK1/2 seemed necessary for NO* production early (<5 min) after H(2)O(2) addition, whereas PI 3-kinase/Akt was more important at later time points [18].
• Recently, insulin-like growth factor-1 (IGF-1) was shown to enhance retinal endothelial glucose transport in a process that is dependent on protein kinase C (PKC) and phosphatidylinositol-3 kinase (PI3 kinase) [19].
• LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3'-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner [20].
• We found that the PI 3-kinase heterodimer consisting of the regulatory and catalytic subunits was associated essentially with the subplasmalemmal cytoskeleton in both resting and nicotine-stimulated chromaffin cells [21].

Analytical, diagnostic and therapeutic context of PIK3R1

• PI-3K activity in capsule-epithelium and fiber cell layers was determined after immunoprecipitation with antibodies against p85, the regulatory subunit of PI-3K [15].
• The amount of PI 3-kinase in membrane and cytosol fractions was determined by densitometry of immunoblots [22].

References