Affinage

PIK3R1

Phosphatidylinositol 3-kinase regulatory subunit alpha · UniProt P27986

Length
724 aa
Mass
83.6 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIK3R1 encodes p85alpha, the predominant regulatory subunit of class IA PI3K, which binds the p110 catalytic subunit to stabilize and constitutively inhibit it while coupling its activation to phosphotyrosine-containing receptors and adaptors such as IRS proteins (PMID:9065454, PMID:21478295, PMID:28167755). The inhibitory function is mediated by the nSH2, iSH2, and cSH2 domains contacting p110; disruption of these contacts by deletions or truncations in the iSH2/nSH2 region releases p110 from inhibition and drives constitutive lipid-kinase activity (PMID:11606375, PMID:21478295, PMID:28167755, PMID:31831213). The gene is functionally pleiotropic: full-length p85alpha forms homodimers through SH3-proline-rich and BH-BH (and cSH2-cSH2) intermolecular contacts, and these p110-free dimers bind, stabilize, and enhance the activity of PTEN, so that loss of p85alpha or its dimerization destabilizes PTEN and de-represses PI3K/AKT signaling (PMID:21984976, PMID:26222500, PMID:10212202, PMID:26475863). Beyond its canonical lipid-kinase scaffold role, p85alpha carries BH-domain GAP activity toward Rab5/Rab4 and Cdc42/Rac1 that controls receptor (PDGFR) trafficking and degradation (PMID:15377662), drives PI3K-independent JNK activation via Cdc42/MKK4 in insulin resistance and ER stress (PMID:14504291, PMID:17283057), and promotes nuclear translocation of XBP-1s to resolve ER stress (PMID:20348926, PMID:24395790). Genetically, p85alpha is required for B-cell development, thymocyte beta-selection, NK and macrophage function, mast-cell and osteoclast signaling, and for insulin-stimulated GLUT4-mediated glucose uptake, where its dosage tunes metabolic sensitivity (PMID:9888855, PMID:9988280, PMID:11781359, PMID:15769893, PMID:18809581, PMID:17237381). Heterozygous loss-of-function splice/truncation mutations cause the immunodeficiency APDS2 (via failed inhibition of p110delta) and SHORT syndrome (via disrupted IRS1 association and reduced PI3K-AKT-mTOR signaling), while iSH2/nSH2 gain-of-function mutations constitutively activate PI3K in cancer (PMID:23810382, PMID:25488983, PMID:28167755, PMID:31831213, PMID:27766312). Its activity is further modulated by post-translational modification, including TRAF6-mediated K63 ubiquitination on Lys513/519 promoting TGF-beta receptor coupling, RBX1/NLRP6-driven K256 ubiquitination targeting it for autophagic degradation, and PKA phosphorylation on Ser83 integrating cAMP signaling (PMID:28676490, PMID:22366926, PMID:37770465).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Establishing that PIK3R1 generates multiple regulatory isoforms with distinct receptor-coupling properties answered how a single gene tunes PI3K responsiveness to insulin.

    Evidence Expression cloning with 32P-IRS-1, co-IP, and PI3K activity assays defining p85alpha/p55alpha/p50alpha isoforms

    PMID:9065454

    Open questions at the time
    • Tissue-specific physiological roles of each isoform not resolved
    • Structural basis of differential IRS-1 affinity not defined
  2. 1999 High

    Genetic ablation in mice defined the in vivo cellular requirements for p85alpha, separating an essential role in B-cell development from dispensability in T-cell development.

    Evidence RAG2 blastocyst complementation with p85alpha/p55alpha/p50alpha knockout mice and lymphocyte functional readouts

    PMID:9888855

    Open questions at the time
    • Molecular signal downstream of receptors not mapped
    • Does not address adaptor vs catalytic-scaffold contribution
  3. 1999 High

    Demonstrating that p85alpha dosage controls insulin sensitivity revealed the regulatory subunit as a rate-limiting tuner of metabolic PI3K signaling rather than merely a permissive scaffold.

    Evidence Targeted knockout mice with insulin-stimulated PI3K activity, PIP3 measurement, and GLUT4 fractionation; later confirmed by heterozygous models

    PMID:11781359 PMID:9988280

    Open questions at the time
    • Mechanism of isoform switch (p85alpha to p50alpha) not fully defined
    • Liver vs muscle vs adipose contributions partly separable
  4. 1999 High

    Mapping the p85alpha homodimerization interfaces established that the protein self-associates independently of SH2 ligand binding, anticipating a p110-free pool.

    Evidence Deletion/point mutants, native PAGE, and competition experiments in vitro and in vivo

    PMID:10212202

    Open questions at the time
    • Functional consequence of dimerization not yet known at this stage
    • Stoichiometry in cells not quantified
  5. 2001 High

    Finding constitutively activating iSH2 deletions in tumors reclassified PIK3R1 as an oncogene, not solely a negative regulator.

    Evidence Mutation analysis of primary colon/ovarian tumors plus PI3K activity assay of mutant protein

    PMID:11606375

    Open questions at the time
    • Precise structural mechanism of activation deferred to later HDX-MS work
    • Frequency across cancer types not established here
  6. 2003 High

    Showing p85alpha is required for insulin-stimulated JNK activation via Cdc42/MKK4 uncovered a PI3K-catalysis-independent signaling output of the regulatory subunit.

    Evidence p85alpha-/- brown adipocyte lines with reconstitution by domain mutants and JNK/Akt/glucose-uptake readouts

    PMID:14504291

    Open questions at the time
    • Direct biochemical link between p85alpha and Cdc42 not reconstituted
    • Physiological relevance addressed later in insulin resistance
  7. 2004 High

    Identifying BH-domain GAP activity toward Rab5/Rab4/Cdc42/Rac1 assigned p85alpha a direct role in receptor trafficking distinct from PI3K regulation.

    Evidence In vitro GAP assays with purified protein, direct Rab5 binding, and BH-mutant PDGFR degradation assays

    PMID:15377662

    Open questions at the time
    • Cellular GAP targets in vivo not exhaustively validated
    • Regulation of the GAP activity unknown
  8. 2006 High

    Defining Galpha(q) as a GTP-dependent binder of the p110alpha/p85alpha complex linked GPCR signaling to PI3K regulation via competition with Ras.

    Evidence Purified-protein fluorescence spectroscopy, deletion-mutant co-precipitation, and constitutively active Galpha(q) signaling assays

    PMID:16268778

    Open questions at the time
    • Physiological GPCR contexts not established
    • Net signaling outcome (inhibition vs activation) context-dependent
  9. 2010 High

    Linking insulin-disrupted p85 monomers to XBP-1s nuclear translocation established a non-catalytic role in resolving ER stress.

    Evidence Reciprocal Co-IP, nuclear fractionation, and in vivo p85 overexpression rescue in ob/ob liver

    PMID:20348926

    Open questions at the time
    • Direct binding region on XBP-1s not mapped
    • Relationship to dimer-monomer equilibrium not quantified
  10. 2011 High

    Distinguishing gain-of-function SH2-domain mutations from loss-of-binding truncations clarified that PIK3R1 cancer mutations act by p110 retention with failed inhibition.

    Evidence Stable mutant expression in U2OS cells with p110alpha co-IP and phospho-AKT readout

    PMID:21478295

    Open questions at the time
    • Quantitative activation per mutant not measured biochemically here
    • Isoform selectivity (p110alpha vs delta) addressed later
  11. 2011 High

    Discovering that p85alpha dimers bind and stabilize PTEN defined a second tumor-suppressive axis lost in cancer mutations.

    Evidence Co-IP of p85alpha dimer-PTEN complex with functional signaling assays across multiple mutations

    PMID:21984976

    Open questions at the time
    • Mechanism of PTEN protection deferred to later reconstitution
    • In vivo contribution to tumor suppression not quantified
  12. 2013 Medium

    Identifying heterozygous PIK3R1 mutations as causal for SHORT syndrome established a human disease of reduced PI3K-AKT-mTOR signaling.

    Evidence Whole-exome/Sanger sequencing across families with downstream S6 phosphorylation assay in patient lymphoblastoid cells

    PMID:23810382

    Open questions at the time
    • Single downstream marker (S6) assayed
    • Mechanism narrowed to IRS1 association only in later work
  13. 2014 High

    Showing that immunodeficiency-causing splice mutations delete inhibitory iSH2/p110-binding residues established APDS2 as a gain-of-function disease via failed p110delta restraint.

    Evidence Patient T-cell studies, mutant overexpression, complex analysis, and PI3Kdelta-inhibitor rescue

    PMID:25133428 PMID:25488983

    Open questions at the time
    • Isoform-specific quantitative activation defined later by HDX-MS
    • Variability across mutations not fully resolved
  14. 2014 High

    Multiple 2014 reports revealed unexpected nuclear/scaffolding roles for p85alpha and its truncation mutants in immune and oncogenic signaling beyond PI3K.

    Evidence Co-IP, nuclear fractionation, and signaling assays for p85alpha-OPN-i/Bcl-6, BRD7 competition for p85, and nuclear JNK/ERK scaffolding by R348*/L370fs mutants

    PMID:24657164 PMID:25284480 PMID:25436971

    Open questions at the time
    • How nuclear translocation is regulated for wild-type vs mutant p85alpha incomplete
    • Generality of scaffolding roles across cell types unknown
  15. 2015 High

    Structural and biophysical characterization of the reversible p85alpha homodimer and its selective binding to unphosphorylated PTEN defined the mechanism protecting PTEN from WWP2-mediated degradation.

    Evidence AUC, FFS, SAXS, cross-linking, biochemical pulldown, in vitro PTEN phosphatase and degradation assays with domain mutants

    PMID:26222500 PMID:26475863

    Open questions at the time
    • In vivo concentration-dependence of dimer-monomer switch not measured
    • Crosstalk between p110 binding and PTEN binding only partly resolved
  16. 2017 High

    Quantitative biochemistry resolved that APDS2-type iSH2 deletions hyperactivate p110delta far more than p110alpha by simultaneously disrupting nSH2/iSH2/cSH2 inhibitory contacts.

    Evidence Reconstituted kinase assays with HDX-MS comparing p110alpha vs p110delta activation; idelalisib sensitivity

    PMID:28167755

    Open questions at the time
    • Cellular consequences of isoform-selective activation not modeled here
    • Other p85 contact regions not exhaustively mapped
  17. 2017 High

    Demonstrating TRAF6-mediated K63 ubiquitination of p85alpha at Lys513/519 revealed a ubiquitin-dependent, kinase-independent route to TGF-beta receptor coupling and motility.

    Evidence PLA, Co-IP, site-specific ubiquitination mutagenesis, migration assays, and tumor tissue analysis

    PMID:28676490

    Open questions at the time
    • Deubiquitinase counterpart not identified
    • Generality beyond TGF-beta context unknown
  18. 2019 High

    Biochemical dissection of additional cancer mutations distinguished iSH2 truncations that broadly de-repress p110alpha from cSH2 mutations that reduce RTK responsiveness.

    Evidence Reconstituted kinase assays with HDX-MS on Q572* and R649W mutants

    PMID:31831213

    Open questions at the time
    • Cellular and clinical correlates of each mutant not established
    • Crosstalk with PTEN-binding function not tested
  19. 2023 High

    Identifying NLRP6/RBX1-driven K256 ubiquitination and OPTN-mediated autophagic degradation of p85alpha defined a turnover mechanism whose loss destabilizes PTEN and activates PI3K/AKT.

    Evidence Co-IP, K256 site-specific ubiquitination mutagenesis, autophagy flux, OPTN interaction, PTEN stability, and tumor xenograft

    PMID:37770465

    Open questions at the time
    • Physiological signals triggering this degradation unclear
    • Interplay with TRAF6 ubiquitination not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple p85alpha functions—p110 inhibition, PTEN stabilization, GAP activity, nuclear scaffolding, and ubiquitin/phosphorylation control—are coordinated within a single cell and dynamically partitioned between catalytic and non-catalytic pools remains unresolved.
  • No integrated model of how dimer-monomer equilibrium routes p85alpha among p110, PTEN, and nuclear partners
  • Quantitative cellular stoichiometry of competing complexes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9612973 Autophagy 1
Partners
BRD7IRS1PIK3CAPIK3CDPTENRBX1TRAF6XBP1
Complex memberships
class IA PI3K (p85alpha-p110alpha/p110delta)p85alpha homodimer

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Genetic disruption of p85alpha (and its splice variants p55alpha/p50alpha) in mice causes defects in B cell development and proliferation, with reduced peripheral mature B cells and decreased proliferative responses to anti-IgM, anti-CD40, and LPS, while T cell development remains normal, demonstrating a specific role for PIK3R1 in B cell signaling. RAG2-deficient blastocyst complementation system with p85alpha-p55alpha-p50alpha knockout mice Science High 9888855
1999 Pik3r1-/- mice show increased insulin sensitivity and hypoglycemia due to increased glucose transport in skeletal muscle and adipocytes; the isoform switch from p85alpha to p50alpha in knockout mice is associated with increased PtdIns(3,4,5)P3 generation and facilitated Glut4 translocation from low-density microsomes to the plasma membrane. Targeted gene disruption in mice; insulin-stimulated PI3K activity assay; PtdIns(3,4,5)P3 measurement; subcellular fractionation of Glut4 Nature genetics High 9988280
2001 Somatic deletions in the inter-SH2 region of PIK3R1 proximal to the Ser608 autoregulatory site (e.g., a 23-amino-acid deletion) result in constitutive PI3K activation, establishing PIK3R1 as an oncogene in colon and ovarian tumors. SSCP/heteroduplex mutation analysis of primary tumors; expression of mutant p85alpha protein in cells with PI3K activity assay Cancer research High 11606375
2002 Heterozygous disruption of Pik3r1 reduces free p85alpha levels, restores the molecular balance between p85, p110, and IRS proteins, maintains normal PI3K activation while increasing insulin-stimulated Akt activity, and improves glucose tolerance and insulin sensitivity; this protects insulin-resistant mice from developing diabetes. Heterozygous Pik3r1 knockout in normal and insulin-resistant mice; PI3K activity assay; Akt phosphorylation; glucose tolerance tests The Journal of clinical investigation High 11781359
2003 p85alpha-/- brown adipocyte cells show 70% reduction in p85 protein with parallel reduction of p110, 50% decrease in PI3K activity, and 30% decrease in Akt activity leading to decreased insulin-induced glucose uptake; p85alpha (but not p85beta) is required for insulin-stimulated JNK activation via cdc42 and MKK4, demonstrating a PI3K-independent signaling function. Gene-disrupted brown adipocyte cell lines; PI3K activity assay; Akt phosphorylation; glucose uptake; JNK activity; reconstitution with p85 mutants The Journal of biological chemistry High 14504291
2004 p85alpha possesses GTPase-activating protein (GAP) activity toward Rab5, Rab4, Cdc42, and Rac1 (with little activity toward Rab11), mediated by its BH domain; purified recombinant p85alpha directly binds Rab5; cells expressing BH domain mutants of p85 show reduced PDGFR degradation rates and sustained MAPK and Akt pathway activation. In vitro GAP assay with purified recombinant proteins; direct binding assay; BH domain mutant expression in cells; PDGFR degradation assay The Journal of biological chemistry High 15377662
2005 p85alpha-/- macrophages show 50% reduction in proliferation in response to M-CSF and GM-CSF, reduced migration and adhesion on fibronectin and VCAM-1, and defective phagocytosis; these are associated with reduced Akt and Rac activation (but not Erk activation), demonstrating a specific role for p85alpha in actin- and growth-based macrophage functions. Bone marrow-derived macrophages from p85alpha-/- mice; proliferation assays; wound-healing and chemotaxis assays; phagocytosis assay; Akt/Rac/Erk phosphorylation Blood High 15769893
1997 The p85alpha gene generates three regulatory subunit isoforms (p85alpha, p55alpha, p50alpha) via alternative splicing; p50alpha forms heterodimers with p110 but uniquely with both wortmannin-sensitive and wortmannin-insensitive forms, exhibits markedly higher capacity for PI3K activation by insulin, and has higher affinity for tyrosine-phosphorylated IRS-1 than p85alpha or p55alpha. Expression cloning using 32P-labeled IRS-1; Northern blotting; co-immunoprecipitation; PI3K activity assay; wortmannin labeling The Journal of biological chemistry High 9065454
2010 p85alpha and p85beta form heterodimers that are disrupted by insulin treatment; the resulting p85 monomers interact with and increase nuclear translocation of the spliced form of XBP-1 (XBP-1s), promoting resolution of ER stress; this interaction is lost in ob/ob mice and restored by p85 overexpression in liver. Co-immunoprecipitation; nuclear fractionation; p85alpha/p85beta overexpression in ob/ob mice liver; XBP-1s nuclear localization assay Nature medicine High 20348926
2011 PIK3R1 mutations in the nSH2 and iSH2 domains (e.g., delH450-E451, delK459, delY463-L466, delR574-T576, N564D) bind p110alpha and increase pAKT(Ser473) levels, demonstrating gain-of-function PI3K activation; truncation mutations (R348X, K511VfsX2) do not bind p110alpha and show no change in pAKT. Stable expression of mutant p85alpha in U2OS cells; co-immunoprecipitation of p110alpha; Western blot of phospho-AKT(Ser473) Cancer research High 21478295
2011 Multiple PIK3R1 and PIK3R2 mutations demonstrate gain-of-function PI3K pathway activation; p85alpha dimers bind and stabilize PTEN, and disruption of this interaction by mutations leads to PTEN destabilization and pathway activation, revealing a novel regulatory mechanism. Functional characterization of mutant proteins; co-immunoprecipitation of p85alpha dimers with PTEN; PI3K pathway signaling assays Cancer discovery High 21984976
2013 Heterozygous mutations in PIK3R1 (including c.1906_1907insC and c.1945C>T p.Arg649Trp) cause SHORT syndrome; functional studies in lymphoblastoid cells with the PIK3R1 frameshift mutation show decreased phosphorylation of the downstream S6 target, indicating downregulation of PI3K-AKT-mTOR pathway signaling. Whole-exome sequencing; Sanger sequencing; functional phosphorylation assay in patient-derived lymphoblastoid cells American journal of human genetics Medium 23810382
2014 A heterozygous splice site mutation in PIK3R1 (causing deletion of residues 434-475 in the inter-SH2 domain) activates PI3K signaling in T cells due to qualitative and quantitative binding changes in the p85alpha-p110delta complex and failure of the C-terminal region to properly inhibit p110delta catalytic activity. Patient cell studies; T cell overexpression of mutant p85alpha; PI3K signaling assays; p85alpha-p110delta complex analysis The Journal of experimental medicine High 25488983
2014 Two heterozygous PIK3R1 splice site mutations causing deletion of exon 10 (part of the p110-binding domain) produce a shortened p85alpha protein that causes elevated AKT phosphorylation in patient T cell blasts, consistent with loss of p85alpha-mediated inhibition of p110 activity. Whole-exome sequencing; Western blot of phospho-AKT in patient T cell blasts; PI3Kδ inhibitor rescue experiment The Journal of clinical investigation Medium 25133428
2014 ICOS activation in CD4+ T cells promotes interaction of p85alpha with intracellular osteopontin (OPN-i), followed by OPN-i nuclear translocation, interaction with Bcl-6, and protection of Bcl-6 from ubiquitin-dependent proteasomal degradation, sustaining TFH and TFR cell differentiation. Co-immunoprecipitation; nuclear fractionation; Bcl-6 stability assay; genetic loss-of-function studies in TFH/TFR cells Nature immunology High 25436971
2014 BRD7 binds to the iSH2 domain of p85alpha and facilitates nuclear translocation of p85alpha; BRD7-dependent depletion of p85 from the cytosol impairs p85/p110 complex formation, decreasing p110 protein levels and PI3K pathway signaling; BRD7 and p110 compete for p85 binding. Co-immunoprecipitation; nuclear fractionation; RNAi knockdown; Akt phosphorylation assay Molecular cell High 24657164
2014 Naturally occurring PIK3R1 truncation mutations PIK3R1(R348*) and PIK3R1(L370fs) localize to the nucleus (unlike wild-type p85alpha) and unexpectedly increase JNK and ERK phosphorylation; these mutant proteins scaffold multiple JNK pathway components in the nucleus to facilitate nuclear JNK pathway activation. Expression of mutant PIK3R1 in cancer cells; nuclear localization studies; JNK/ERK phosphorylation assays; in vitro and in vivo MEK/JNK inhibitor response Cancer cell High 25284480
2015 p110alpha-free p85alpha homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN; homodimeric p85alpha protects PTEN from E3 ligase WWP2-mediated proteasomal degradation and enhances PTEN lipid phosphatase activity and membrane association; cancer-derived oncogenic p85alpha mutations disrupt homodimerization or the PTEN interaction surface. Biochemical pulldown; co-immunoprecipitation; in vitro PTEN lipid phosphatase assay; proteasomal degradation assay; domain mutant analysis eLife High 26222500
1999 p85alpha dimerizes via intermolecular SH3 domain-proline-rich motif interactions and BH-BH domain interactions both in vitro and in vivo; competition experiments show these are intermolecular interactions; binding of SH2 domain ligands does not affect the dimeric state. Deletion and point mutants; native PAGE for apparent molecular mass; competition experiments; in vitro and in vivo dimerization assays The Journal of biological chemistry High 10212202
2008 Crystal structure of p110alpha/p85alpha reveals that oncogenic mutations predominantly occur at interfaces between p110 domains and between p110 and p85 domains; these mutations disrupt stabilizing interactions at the p110alpha-p85alpha interface; the iSH2 domain of p85alpha mediates membrane interaction. X-ray crystallography; structural analysis of oncogenic mutation positions Cell cycle High 18418043
2017 TRAF6 polyubiquitylates p85alpha on Lys513 and Lys519 in the iSH2 domain (Lys63-linked) in response to TGF-beta, promoting formation of a complex between TGF-beta type I receptor (TbetaRI) and p85alpha, leading to PI3K and AKT activation and cell motility; this activation is independent of TbetaRI kinase activity. In situ proximity ligation assay; co-immunoprecipitation; ubiquitination assay; mutagenesis of Lys513/Lys519; cell migration assay; prostate cancer tissue analysis Science signaling High 28676490
2017 APDS2 mutation in p85alpha (deletion 434-475) leads to >300-fold basal activation of p110delta but only ~2-fold activation of p110alpha when associated with mutated p85alpha; the mutation disrupts inhibitory interactions from the nSH2, iSH2, and cSH2 domains of p85; all APDS mutations are inhibited by idelalisib. Biochemical kinase assays; hydrogen-deuterium exchange mass spectrometry; comparison of p110alpha vs p110delta activation by mutant p85alpha Proceedings of the National Academy of Sciences of the United States of America High 28167755
2019 The oncogenic PIK3R1 Q572* truncation in the iSH2 domain disrupts all p85-inhibitory inputs and hyper-activates p110alpha more than p110delta; the R649W mutation in the cSH2 domain of PIK3R1 decreases sensitivity to activation by receptor tyrosine kinases. Biochemical kinase assays; hydrogen-deuterium exchange mass spectrometry Structure High 31831213
2015 p85alpha undergoes rapidly reversible concentration-dependent monomer-dimer assembly in vitro and in vivo; dimerization involves both SH3-PR1 and cSH2-cSH2 intermolecular interactions; the structural architecture of the p85alpha homodimer was determined by integrative methods including SAXS and chemical cross-linking. Analytical ultracentrifugation; fluorescence fluctuation spectroscopy (in vivo); SAXS; chemical cross-linking; integrative structure determination The Journal of biological chemistry High 26475863
2006 Activated Galpha(q) directly binds p110alpha/p85alpha PI3K (not p110gamma) in a GTP-dependent manner with approximately 7-fold stronger affinity than GDP-bound Galpha(q); Galpha(q) competes with Ras for binding to p110alpha/p85alpha by binding to the p85-binding domain of p110alpha (not the Ras-binding domain), inhibiting Ras activation of the PI3K/Akt pathway. Purified protein fluorescence spectroscopy; co-precipitation with deletion mutants; constitutively active Galpha(q)Q209L expression; PI3K/Akt signaling assay The Biochemical journal High 16268778
2005 The N-terminal SH2, C-terminal SH2, and SH3 domains of p85alpha are required for interaction with the BCR/ABL protein network; a triple domain mutant of p85alpha (p85mut) disrupts binding to BCR/ABL and other fusion tyrosine kinases while retaining p110alpha binding, reducing PI3K and Akt activation and inhibiting BCR/ABL-dependent leukemogenic transformation. Point mutations in SH2 and SH3 domains; co-immunoprecipitation; PI3K activity assay; Akt phosphorylation; hematopoietic transformation assay; SCID mouse model Molecular and cellular biology High 16135792
2007 p85alpha (but not p85beta) is required for JNK activation in states of insulin resistance (high-fat diet-induced obesity, JNK1 overexpression); p85alpha activates JNK via cdc42 and MKK4, independently of its role as a PI3K heterodimer component and only in response to insulin and ER stress-inducing stimuli; both an intact N terminus and functional SH2 domains are required. p85alpha-/- and p85beta-/- cell lines; JNK activity assay; p85alpha domain mutant reconstitution; cdc42/MKK4 epistasis Molecular and cellular biology High 17283057
2008 p85alpha (regulatory) and p110beta (catalytic) isoforms, but not p110alpha, are specifically required for androgen-stimulated androgen receptor transactivation and cell proliferation in prostate cancer cells; p110beta lipid kinase activity (not protein kinase activity) is required; p110beta is indispensable for androgen-induced AR-DNA interaction. siRNA knockdown of p85alpha/p110alpha/p110beta; AR transactivation assay; chromatin immunoprecipitation; tumor xenograft Oncogene Medium 18372911
2008 p85alpha deficiency in osteoclasts results in impaired growth, differentiation, adhesion, and migration via integrin alphavbeta3, with reduced Akt and Erk1/2 activation; full-length p85alpha (but not SH3-domain-deleted version) is required for osteoclast maturation; p85alpha regulates expression of MITF, TRAP, cathepsin K, and beta3 integrin. p85alpha-/- osteoclast progenitors; in vivo bone histomorphometry; in vitro differentiation/adhesion/migration assays; microarray; reconstitution with SH3-deleted mutant Molecular and cellular biology High 18809581
2007 IREM-1 (CD300f) recruits p85alpha of PI3K (via tyrosine residues Y236 and Y263) and SHP-1 upon immunoprecipitation; PI3K recruitment through these residues (when Y205 and Y249 ITIM sites are mutated) drives degranulation in RBL cells, demonstrating dual inhibitory/activating signaling capacity of IREM-1 depending on p85alpha recruitment. Immunoprecipitation in transfected cells and U937 cells; IREM-1 tyrosine mutants; RBL cell degranulation assay; PI3K inhibitor treatment Journal of immunology Medium 17202342
2008 p85alpha deficiency impairs NK cell lineage commitment (reducing NK cellularity in bone marrow and liver), Ly49 subset specification, NKG2D and NK1.1 receptor-mediated cytokine/chemokine generation, and NK-mediated cytotoxicity against tumor cells. p85alpha-/- mice; flow cytometric analysis of NK subset specification; NK cytotoxicity assays; cytokine measurement Genes and immunity Medium 18548087
2007 p85alpha deficiency specifically impairs Kit ligand/SCF-induced (but not FcepsilonRI-initiated) mast cell secretory granule exocytosis, proliferation, and Akt phosphorylation, demonstrating receptor-specific usage of different PI3K family members in a single cell type. p85alpha-/- mast cells; Kit and FcepsilonRI cross-linking; exocytosis and proliferation assays; Akt phosphorylation; PI3K inhibitor (LY294002) The Journal of biological chemistry High 10681597
2012 PIK3R1 loss in ovarian cancer cells activates AKT through enhanced p110alpha kinase activity, decreased PTEN levels, and p110-independent JAK2/STAT3 signaling through deregulated Gab2 phosphorylation; PIK3R1 loss relieves negative inhibition on AKT and promotes assembly of JAK2/STAT3 signalosome. PIK3R1 knockdown in ovarian cancer cells; phosphoproteomics; Gab2 phosphorylation analysis; JAK2/STAT3 signaling assays; combination inhibitor treatment Nature communications High 30755611
1993 Both p85alpha and p85beta isoforms associate with p110 and PI3K activity in T cells; upon TCR/CD3 or PKC stimulation, the p110 complexed to p85alpha becomes rapidly phosphorylated on serine, while p85beta undergoes rapid increase in threonine phosphorylation, revealing differential regulation of the two PI3K isoforms. Phosphopeptide pulldown; isoform-specific monoclonal antibodies; T cell activation assays; phosphorylation analysis The Journal of biological chemistry Medium 8388374
2014 p85alpha deficiency in osteoclast progenitors (using p85alpha-/- mice) demonstrates that genetic disruption of p85alpha but not p85beta normalizes KITD814V oncogenic KIT-induced ligand-independent hyperproliferation and promiscuous cytokine responses in HSC/Ps and mast cell progenitors. Genetic disruption of p85alpha vs p85beta in KITD814V-expressing hematopoietic cells; proliferation assays; Rac inhibitor and rapamycin treatment Blood Medium 17483298
2016 C-terminal PIK3R1 mutations (SHORT syndrome) show severely reduced insulin-stimulated association of mutant but not WT p85alpha with IRS1; mutant p85alpha overexpression in 3T3-L1 preadipocytes attenuates insulin-induced AKT phosphorylation and adipocyte differentiation. Patient-derived cells (p.Tyr657X mutation); co-immunoprecipitation of p85alpha-IRS1; mutant p85alpha overexpression in 3T3-L1 cells; AKT phosphorylation; adipocyte differentiation assay JCI insight Medium 27766312
2021 CBL mutations drive PI3K/AKT signaling via increased LYN activation and interaction with mutant CBL, leading to enhanced CBL phosphorylation, PIK3R1 recruitment, and downstream PI3K/AKT signaling; LYN inhibition (genetic or dasatinib) reduces CBL-PIK3R1 interaction and PI3K/AKT signaling. Global mass spectrometry phosphoproteomics; CBL interactome by MS; functional signaling assays; genetic ablation and dasatinib inhibition of LYN; in vitro and in vivo antiproliferative assays Blood High 33512474
2012 PKA phosphorylates p85alpha on Ser83 adjacent to the N-terminal SH3 domain in vivo and in vitro; Ser83 phosphorylation is crucial for synergistic RARα/p85alpha binding induced by cAMP/RA co-treatment, and controls MCF7 cell proliferation, RA-induced inhibition of proliferation, migration, and RA-induced reduction of motility. PKA phosphorylation assay in vivo and in vitro; Ser83Ala and Ser83Asp p85alpha mutants; co-immunoprecipitation of RARα/p85alpha; cell growth and migration assays International journal of oncology Medium 22366926
2016 p85alpha promotes nucleolin (NCL) transcription via c-Jun activation; NCL binds EGFR mRNA and increases its stability; p85alpha thereby upregulates EGFR protein expression and promotes malignant cellular transformation in a PI3K-independent manner. p85alpha knockdown and knockout cells; EGFR mRNA stability assay; NCL overexpression rescue; c-Jun activation analysis Oncotarget Medium 26918608
2023 NLRP6 binds p85alpha and recruits E3 ligase RBX1 to ubiquitinate p85alpha on Lys256; this ubiquitination is recognized by autophagy cargo receptor OPTN, causing selective autophagic degradation of p85alpha, subsequent reduction of PTEN stability, and activation of the PI3K/AKT pathway. Co-immunoprecipitation; ubiquitination assay with site-specific mutagenesis (K256); autophagy flux assay; OPTN interaction; PTEN stability assay; tumor xenograft Nature communications High 37770465
2017 PAK4 specifically interacts with p85alpha (the regulatory subunit of PI3K), and PAK4-deficient pancreatic cancer cells exhibit reduced AKT phosphorylation downstream of HGF signaling, implicating PAK4 in PI3K pathway activation via p85alpha interaction. Co-immunoprecipitation of PAK4 and p85alpha; PAK4 knockdown; AKT phosphorylation assay; HGF stimulation Scientific reports Medium 28205613
2014 p85alpha deficiency in beta-cells markedly delays onset and severity of ER stress-induced diabetic phenotype in Akita+/- mice by decreasing activation of ER stress-dependent apoptotic pathways and preserving beta-cell mass; this is linked to p85alpha's role in promoting nuclear localization of XBP-1. p85alpha-deficient Akita+/- mice; beta-cell mass quantification; ER stress pathway assays; XBP-1 nuclear localization Proceedings of the National Academy of Sciences of the United States of America Medium 24395790
2007 p85alpha deficiency in thymocytes impairs pre-TCR-controlled beta-selection (DN to DP transition) without affecting positive or negative selection; inhibition of p110delta blocks DN-to-DP transition in fetal thymic organ culture; PTEN deficiency (amplifying PI3K signals) accelerates this transition. p85alpha-/- Rag-2-/- mice with anti-CD3epsilon injection; p110delta inhibitor (IC87114) in fetal thymic organ culture; PTEN-/- thymic organ culture; flow cytometry of thymocyte subsets Journal of immunology High 17237381

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science (New York, N.Y.) 524 9888855
2001 The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer research 403 11606375
2011 High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability. Cancer discovery 398 21984976
2019 Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression. Molecular cancer 337 30927924
1999 Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nature genetics 330 9988280
2006 Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin. Diabetes 289 16873706
2010 The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nature medicine 245 20348926
2014 Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. The Journal of experimental medicine 235 25488983
2002 Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. The Journal of clinical investigation 215 11781359
2014 A human immunodeficiency caused by mutations in the PIK3R1 gene. The Journal of clinical investigation 206 25133428
2017 TGF-β promotes PI3K-AKT signaling and prostate cancer cell migration through the TRAF6-mediated ubiquitylation of p85α. Science signaling 188 28676490
2011 PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer. Cancer research 171 21478295
2003 Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling. The Journal of biological chemistry 165 14504291
2020 circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer. Molecular cancer 153 32366257
2013 Mutations in PIK3R1 cause SHORT syndrome. American journal of human genetics 148 23810382
1997 p85alpha gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and p85alpha, with different PI 3-kinase activity elevating responses to insulin. The Journal of biological chemistry 143 9065454
2007 Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. Diabetes 134 17363744
2018 microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene 125 29527004
2000 A specific function for phosphatidylinositol 3-kinase alpha (p85alpha-p110alpha) in cell survival and for phosphatidylinositol 3-kinase beta (p85alpha-p110beta) in de novo DNA synthesis of human colon carcinoma cells. Oncogene 124 11042696
2018 Characterization of PIK3CA and PIK3R1 somatic mutations in Chinese breast cancer patients. Nature communications 123 29636477
2014 A p85α-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells. Nature immunology 121 25436971
2019 The Opposing Roles of PIK3R1/p85α and PIK3R2/p85β in Cancer. Trends in cancer 113 30961830
2017 Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b. Oncogene 106 28394344
2017 Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1. Proceedings of the National Academy of Sciences of the United States of America 98 28167755
2015 PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer. International journal of oncology 98 26676464
2011 Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells. Oncotarget 98 22064833
2004 The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins. The Journal of biological chemistry 95 15377662
2011 A systematic study of gene mutations in urothelial carcinoma; inactivating mutations in TSC2 and PIK3R1. PloS one 93 21533174
2014 MicroRNA-486-5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1. The FEBS journal 87 25475121
1993 Divergent regulation of phosphatidylinositol 3-kinase P85 alpha and P85 beta isoforms upon T cell activation. The Journal of biological chemistry 86 8388374
2022 Pan-cancer analysis on the role of PIK3R1 and PIK3R2 in human tumors. Scientific reports 85 35395865
2014 Naturally occurring neomorphic PIK3R1 mutations activate the MAPK pathway, dictating therapeutic response to MAPK pathway inhibitors. Cancer cell 79 25284480
2012 Multiple roles for the p85α isoform in the regulation and function of PI3K signalling and receptor trafficking. The Biochemical journal 79 22168437
2023 The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity. International journal of molecular sciences 78 37628845
2014 BRD7, a tumor suppressor, interacts with p85α and regulates PI3K activity. Molecular cell 76 24657164
2015 Regulation of the PI3K pathway through a p85α monomer-homodimer equilibrium. eLife 74 26222500
2008 Phosphoinositide 3-OH kinase p85alpha and p110beta are essential for androgen receptor transactivation and tumor progression in prostate cancers. Oncogene 72 18372911
2000 Impaired kit- but not FcepsilonRI-initiated mast cell activation in the absence of phosphoinositide 3-kinase p85alpha gene products. The Journal of biological chemistry 68 10681597
2008 Insights into the oncogenic effects of PIK3CA mutations from the structure of p110alpha/p85alpha. Cell cycle (Georgetown, Tex.) 65 18418043
2007 The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance. Molecular and cellular biology 64 17283057
2019 MiR-486-5p Serves as a Good Biomarker in Nonsmall Cell Lung Cancer and Suppresses Cell Growth With the Involvement of a Target PIK3R1. Frontiers in genetics 60 31402930
2016 Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations. JCI insight 57 27766312
2020 Glyphosate induces lymphocyte cell dysfunction and apoptosis via regulation of miR-203 targeting of PIK3R1 in common carp (Cyprinus carpio L.). Fish & shellfish immunology 56 32217141
2005 p85alpha subunit of class IA PI-3 kinase is crucial for macrophage growth and migration. Blood 56 15769893
2007 The IREM-1 (CD300f) inhibitory receptor associates with the p85alpha subunit of phosphoinositide 3-kinase. Journal of immunology (Baltimore, Md. : 1950) 53 17202342
2016 Targeting therapeutic liabilities engendered by PIK3R1 mutations for cancer treatment. Pharmacogenomics 51 26807692
2012 Attenuated Pik3r1 expression prevents insulin resistance and adipose tissue macrophage accumulation in diet-induced obese mice. Diabetes 49 22698915
2012 Somatic mutations of PIK3R1 promote gliomagenesis. PloS one 49 23166678
2019 CapG promotes resistance to paclitaxel in breast cancer through transactivation of PIK3R1/P50. Theranostics 48 31660072
2016 Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1. Scientific reports 48 26972586
2017 FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients. Journal of experimental & clinical cancer research : CR 47 29208003
2019 CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis. Aging 46 31848327
1999 Intermolecular interactions of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase. The Journal of biological chemistry 45 10212202
2021 Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth. Genetics in medicine : official journal of the American College of Medical Genetics 43 34040190
2021 Oral squamous cell carcinoma (OSCC)-derived exosomal MiR-221 targets and regulates phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to promote human umbilical vein endothelial cells migration and tube formation. Bioengineered 43 34098850
2020 Antagonistic effect of selenium on lead-induced neutrophil apoptosis in chickens via miR-16-5p targeting of PiK3R1 and IGF1R. Chemosphere 43 31918102
2022 The Impact of PIK3R1 Mutations and Insulin-PI3K-Glycolytic Pathway Regulation in Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 42 35670774
2020 Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma. Cancer cell international 40 31938022
2008 Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk. Clinical cancer research : an official journal of the American Association for Cancer Research 40 18245521
2021 Exosomal miR-21-5p derived from bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion by targeting PIK3R1. Journal of cellular and molecular medicine 39 34741385
2019 Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer. Nature communications 39 30755611
2024 N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation. Molecular cancer 38 38184597
2017 PAK4 interacts with p85 alpha: implications for pancreatic cancer cell migration. Scientific reports 37 28205613
2015 Oncogenic mutations weaken the interactions that stabilize the p110α-p85α heterodimer in phosphatidylinositol 3-kinase α. The FEBS journal 37 26122737
2018 Overexpression of PIK3R1 promotes hepatocellular carcinoma progression. Biological research 36 30497511
2019 Upregulated gga-miR-16-5p Inhibits the Proliferation Cycle and Promotes the Apoptosis of MG-Infected DF-1 Cells by Repressing PIK3R1-Mediated the PI3K/Akt/NF-κB Pathway to Exert Anti-Inflammatory Effect. International journal of molecular sciences 34 30818821
2006 Galphaq binds to p110alpha/p85alpha phosphoinositide 3-kinase and displaces Ras. The Biochemical journal 34 16268778
2021 CBL mutations drive PI3K/AKT signaling via increased interaction with LYN and PIK3R1. Blood 32 33512474
2013 PIK3R1 mutations in SHORT syndrome. Clinical genetics 32 23980586
2011 Uncommon GNAQ, MMP8, AKT3, EGFR, and PIK3R1 mutations in thyroid cancers. Endocrine pathology 32 21487925
2008 Deletion of PI3K-p85alpha gene impairs lineage commitment, terminal maturation, cytokine generation and cytotoxicity of NK cells. Genes and immunity 31 18548087
2015 p85α is a microRNA target and affects chemosensitivity in pancreatic cancer. The Journal of surgical research 30 25846727
2008 The p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the expression of multiple genes involved in osteoclast maturation and migration. Molecular and cellular biology 30 18809581
2021 Downregulation of miR-128 Ameliorates Ang II-Induced Cardiac Remodeling via SIRT1/PIK3R1 Multiple Targets. Oxidative medicine and cellular longevity 29 34646427
2007 Genetic and pharmacologic evidence implicating the p85 alpha, but not p85 beta, regulatory subunit of PI3K and Rac2 GTPase in regulating oncogenic KIT-induced transformation in acute myeloid leukemia and systemic mastocytosis. Blood 29 17483298
2023 Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2. The Journal of experimental medicine 28 36943234
2020 Exosomal MicroRNA-221-3p Confers Adriamycin Resistance in Breast Cancer Cells by Targeting PIK3R1. Frontiers in oncology 28 32426266
2020 MiR-155 promotes interleukin-1β-induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1-mediated PI3K/Akt pathway. Journal of cellular and molecular medicine 28 32562373
2019 An oncogenic gene, SNRPA1, regulates PIK3R1, VEGFC, MKI67, CDK1 and other genes in colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 31203132
2019 Long noncoding RNA NEAT1 promotes the growth of gastric cancer cells by regulating miR-497-5p/PIK3R1 axis. European review for medical and pharmacological sciences 28 31486491
2019 Defining How Oncogenic and Developmental Mutations of PIK3R1 Alter the Regulation of Class IA Phosphoinositide 3-Kinases. Structure (London, England : 1993) 27 31831213
2014 p85α deficiency protects β-cells from endoplasmic reticulum stress-induced apoptosis. Proceedings of the National Academy of Sciences of the United States of America 27 24395790
2022 miR-351 promotes atherosclerosis in diabetes by inhibiting the ITGB3/PIK3R1/Akt pathway and induces endothelial cell injury and lipid accumulation. Molecular medicine (Cambridge, Mass.) 26 36180828
2020 A novel lncRNA LNC_000052 leads to the dysfunction of osteoporotic BMSCs via the miR-96-5p-PIK3R1 axis. Cell death & disease 26 32968049
2004 Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alpha. International immunology 26 15520044
2023 NLRP6 potentiates PI3K/AKT signalling by promoting autophagic degradation of p85α to drive tumorigenesis. Nature communications 25 37770465
2017 Domain analysis reveals striking functional differences between the regulatory subunits of phosphatidylinositol 3-kinase (PI3K), p85α and p85β. Oncotarget 25 28915558
2005 Phosphatidylinositol 3-kinase p85{alpha} subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: molecular mechanisms and biological consequences. Molecular and cellular biology 25 16135792
2020 Truncation of Pik3r1 causes severe insulin resistance uncoupled from obesity and dyslipidaemia by increased energy expenditure. Molecular metabolism 24 32439336
2020 CircHIPK3/miR-876-5p/PIK3R1 axis regulates regulation proliferation, migration, invasion, and glutaminolysis in gastric cancer cells. Cancer cell international 24 32817745
2007 SHP-2 and PI3-kinase genes PTPN11 and PIK3R1 may influence serum apoB and LDL cholesterol levels in normal women. Atherosclerosis 24 17214991
2024 Unveiling the role of PIK3R1 in cancer: A comprehensive review of regulatory signaling and therapeutic implications. Seminars in cancer biology 23 39197810
2012 The p85α regulatory subunit of PI3K mediates cAMP-PKA and retinoic acid biological effects on MCF7 cell growth and migration. International journal of oncology 23 22366926
2007 The p85alpha regulatory subunit of class IA phosphoinositide 3-kinase regulates beta-selection in thymocyte development. Journal of immunology (Baltimore, Md. : 1950) 23 17237381
2015 Assembly and Molecular Architecture of the Phosphoinositide 3-Kinase p85α Homodimer. The Journal of biological chemistry 22 26475863
2023 PIK3CA and PIK3R1 tumor mutational landscape in a pan-cancer patient cohort and its association with pathway activation and treatment efficacy. Scientific reports 21 36934165
2019 Impact of p85α Alterations in Cancer. Biomolecules 21 30650664
2018 PIK3R1 gene polymorphisms are associated with type 2 diabetes and related features in the Turkish population. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 21 29893513
2016 p85α promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation. Oncotarget 21 26918608
2021 miR-92a promotes cervical cancer cell proliferation, invasion, and migration by directly targeting PIK3R1. Journal of clinical laboratory analysis 18 34216514

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