High impact information on PIK3R1

• However, these insulin-induced events are uniquely controlled by PI3 kinase and PKC-zeta, which act upstream of Aurora A [1].
• PI-3 kinase and IP3: partners in NT3-induced synaptic transmission [2].
• However, neither stimulation of Ca2+ release from intracellular stores by photolysis of caged IP3, nor expression of a constitutively active phosphoinositide-3 kinase (PI3K*) in presynaptic motoneurons alone is sufficient to enhance transmission [3].
• Phospholipase C-gamma and phosphoinositide 3-kinase mediate cytoplasmic signaling in nerve growth cone guidance [4].
• Thus, the checkpoint-mediated activation of XCds1 requires phosphorylation by multiple phosphoinositide 3-kinase-related kinases, protein-protein dissociation, and autophosphorylation [5].

Biological context of PIK3R1

• A constitutively active PI3 kinase partially rescues the Kermit 2/XGIPC loss-of-function phenotype [6].
• In higher eukaryotes, GSK-3 has been implicated in signal transduction pathways downstream of phosphoinositide 3-kinase and mitogen-activated protein kinases [7].
• Phosphatidylinositol 3-kinase (PI3K) has numerous cellular functions, including cell survival and proliferation [8].
• However, non-phosphorylated or bisphosphonotyrosine peptides with the identical amino acid sequence failed to stimulate transport or PI 3-kinase activity [9].
• We show that a bifunctional synthetic peptide containing two YMXM consensus sequences for binding to SH2 domains stimulated both PI 3-kinase activity and deoxyglucose transport when both tyrosine residues were phosphorylated [9].

Anatomical context of PIK3R1

• Pretreatment of these oocytes with wortmannin inhibited insulin-induced activation of PI 3-kinase in vivo [10].
• We find that a class 1A PI3K catalytic activity is required for the definition of trunk mesoderm during the blastula stages, but is less important for endoderm and prechordal plate mesoderm induction or for organiser formation [11].
• These results indicate that alphaPIX is activated by PI3-kinase, and is involved in the receptor mediated signaling leading to the activation of the kinase activity of PAK, and the migration of mesodermal cells on extracellular matrix [12].
• However, our analysis of these pathways in gastrula stage embryos indicates that the MAP kinase pathway is required for Cdx gene expression, whereas the PI-3 kinase pathway is not [13].
• These data suggest that SGK is a PI3K-dependent integrator of insulin and mineralocorticoid actions that interacts with ENaC subunits to control Na+ entry into kidney collecting duct cells [14].

Associations of PIK3R1 with chemical compounds

• PI3 kinase activity was present in immunoprecipitates of the p85 subunit of PI3 kinase from immature oocytes and markedly increased following progesterone stimulation [15].
• Another glutathione S-transferase fusion protein containing the C terminus of XIRS-L and including several putative tyrosine phosphorylation sites is also phosphorylated by IRK in vitro, but it failed to bind PI 3-kinase [10].
• Incubation of oocytes with the PI 3-kinase inhibitor wortmannin inhibited insulin-like growth factor-1-stimulated deoxyglucose uptake [9].
• Taken together, these data argue strongly for a role for PI 3-kinase in the regulation of glucose transport in oocytes [9].
• Treating cells with either wortmannin or LY294002, two structurally different inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase) and with the phospholipase Cgamma (PLCgamma) inhibitor U73122, abolished RA-induced facilitation of synaptic transmission [16].

Other interactions of PIK3R1

• Purified amino-terminal Src homology 2 (SH2) domains of GAP, PLCgamma1 and the p85alpha subunit of PI 3-kinase, as well as the carboxy-terminal SH2 domain of the latter protein and the unique SH2 domain of Grb2, were injected into full grown, stage VI Xenopus laevis oocytes [17].
• In Xenopus, aggregates of mesodermal cells derived from embryos microinjected with alphaPIX significantly increased the peripheral spreading on fibronectin substrate in response to PDGF through PI3-kinase [12].
• We examined the role of Mos, Mek, PI-3 kinase and c-Jun N-terminal kinase (JNK) in progesterone stimulation of GVBD [18].
• The stress-induced changes in eIF4E phosphorylation were totally abrogated by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and were partly inhibited by the phosphoinositide 3-kinase inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin [19].
• Pretreatment with wortmannin, a PI3 K inhibitor, also abolished the ethanol-enhanced EAAT3 activity [20].

Analytical, diagnostic and therapeutic context of PIK3R1

• Conversely, we also examined the effects of microinjection of synthetic peptides designed to interact with Src homology 2 domains of the regulatory subunit of PI 3-kinase on deoxyglucose transport in oocytes [9].
• However, although the H-Ras/PI3K pathway is functional in Xenopus oocytes, it is not the physiological transducer of progesterone responsible for meiotic resumption [21].
• We also estimated the relative importance of the PI 3-kinase pathway by two different methods: 1) coprecipitation of the p85 regulatory subunit with anti-phosphotyrosine antibodies and 2) phosphorylation of PKB on both Ser 473 and Thr 308 residues observed by Western blotting [22].

References