Affinage

IGBP1

Immunoglobulin-binding protein 1 · UniProt P78318

Length
339 aa
Mass
39.2 kDa
Annotated
2026-06-10
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IGBP1 (alpha4) is a noncatalytic regulatory partner of the PP2A catalytic subunit (PP2Ac) that governs PP2Ac stability and directs its phosphatase activity toward distinct substrates to control cell survival, proliferation, signaling, and tissue homeostasis (PMID:15499020, PMID:34998390). Structurally it is an elongated protein whose stable, predominantly α-helical N-terminal TPR-like domain binds PP2Ac and contains an embedded ubiquitin-interacting motif (residues 46–60), while its less-structured C-terminal region engages E3 ligases (PMID:21454489, PMID:16517231). Through the UIM and a C-terminal Mid1-binding domain, IGBP1 acts as an adaptor that bridges PP2Ac to the E3 ligase Mid1 and suppresses PP2Ac polyubiquitination, protecting it from degradation; both the N- and C-terminal domains are required for this protection (PMID:20092282, PMID:21454489). By repressing PP2A-mediated dephosphorylation of c-Jun and p53, IGBP1 prevents transcription-initiated apoptosis and is required for cell viability (PMID:15499020). It directs PP2A-dependent signaling outputs in multiple contexts: it activates Rac1 to promote cell spreading and migration (PMID:17693407), operates a GqPCR-triggered 'PP2A switch' in which an IGBP1–PP2Ac dimer shifts from PI3K to AKT to drive AKT dephosphorylation and JNK-dependent apoptosis (PMID:34998390), sustains mTOR-dependent translation initiation through a positive feedback loop in erythroblasts (PMID:18625885), maintains insulin signaling in adipocytes via a YBX1–PTP1B axis (PMID:36241662), and stabilizes the RNA-binding protein HuR to preserve intestinal epithelial barrier function (PMID:29555726). IGBP1 is required for early T cell development by supporting thymocyte proliferation (PMID:12811850), and is elevated in human cancers where it promotes proliferation and transformation and is suppressed by miR-34b and miR-3941 (PMID:21339737, PMID:28012229).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 Medium

    Establishing the gene's identity and pathway context: human alpha4/IGBP1 was cloned and recognized as a TAP42-related protein, placing it in a rapamycin-sensitive signaling pathway before its mechanism was known.

    Evidence Genomic cloning, Northern blot, antibody detection, and TAP42 sequence alignment

    PMID:9441740

    Open questions at the time
    • Homology to TAP42 inferred function but provided no direct biochemical activity
    • No PP2Ac interaction demonstrated in this study
  2. 2003 High

    Defined the first in vivo requirement: T cell-specific deletion showed IGBP1 is needed for thymocyte proliferation and developmental progression, not for suppressing apoptosis in this lineage.

    Evidence Cre/loxP T cell-specific knockout mice with developmental-stage flow cytometry and proliferation/apoptosis assays

    PMID:12811850

    Open questions at the time
    • Molecular link between IGBP1 and proliferative signaling in thymocytes not resolved
    • PP2A involvement in this phenotype not directly tested
  3. 2004 High

    Identified a core function in cell survival: IGBP1 loss unleashes PP2A-mediated dephosphorylation of c-Jun and p53, driving proapoptotic transcription and death, establishing IGBP1 as a repressor of transcription-initiated apoptosis.

    Evidence Conditional knockout in murine cells with Bcl-xL and translation-inhibitor rescue plus transcriptional profiling

    PMID:15499020

    Open questions at the time
    • How IGBP1 restrains PP2Ac substrate access to c-Jun/p53 not structurally defined
    • Direct dephosphorylation events not biochemically reconstituted
  4. 2006 Medium

    Provided the first solution architecture: IGBP1 is elongated with a stable α-helical N-terminal domain and a less-structured, proteolysis-prone C-terminus, predicting a modular domain organization.

    Evidence SAXS, circular dichroism, and thermal unfolding of recombinant truncation mutants

    PMID:16517231

    Open questions at the time
    • No mutagenesis linking domain features to function
    • Low-resolution envelope only, no atomic model
  5. 2007 High

    Connected IGBP1 to cytoskeletal dynamics: it promotes cell spreading and migration through Rac1 activation, broadening its role beyond survival.

    Evidence Knockout fibroblasts, overexpression, constitutively active Rac1 rescue, GTPase pull-down, and T cell transgenic chemotaxis

    PMID:17693407

    Open questions at the time
    • Mechanism linking IGBP1/PP2A to Rac1 GTP loading not defined
    • GEF/GAP intermediary not identified
  6. 2008 High

    Embedded IGBP1 in a translation-regulatory feedback loop: its mRNA is selectively polysome-recruited downstream of PI3K, and constitutive expression sustains 4EBP/p70S6K phosphorylation, linking IGBP1 to mTOR-dependent translation initiation in erythroblasts.

    Evidence Polysome profiling with microarray, PI3K inhibition, eIF4E overexpression, and constitutive Igbp1 expression in erythroid differentiation

    PMID:18625885

    Open questions at the time
    • Direct biochemical role of IGBP1 in initiation-complex assembly not shown
    • Feedback wiring inferred from gain-of-function
  7. 2009 Medium

    Placed IGBP1 in a regulatory complex with mTOR and STAT1: mTOR inactivation increases IGBP1 association and PP2Ac-dependent STAT1 nuclear accumulation, controlling STAT1-driven gene expression.

    Evidence Reciprocal Co-IP of mTOR-STAT1-IGBP1-PP2Ac complex, siRNA depletion, nuclear fractionation, and gene expression analysis

    PMID:19553685

    Open questions at the time
    • Direct STAT1 dephosphorylation by the complex not demonstrated
    • Single lab, mechanism of mTOR-dependent recruitment unclear
  8. 2010 High

    Defined the ubiquitin-adaptor mechanism: a novel UIM (residues 46–60) lets IGBP1 bind ubiquitin and bridge PP2Ac to the E3 ligase Mid1, with the UIM suppressing PP2Ac polyubiquitination.

    Evidence NMR of IGBP1-ubiquitin interaction, Co-IP of IGBP1/PP2Ac/Mid1, and UIM-deletion ubiquitination assays

    PMID:20092282

    Open questions at the time
    • How UIM occupancy blocks ubiquitin chain extension mechanistically unresolved
    • In vivo physiological consequence of UIM loss not tested in animals
  9. 2010 Medium

    Expanded the C-terminal interactome: IGBP1 binds EDD E3 ligase (independent of the PP2Ac site) and PABP, implicating it in translation-initiation steps downstream of mTOR.

    Evidence Yeast two-hybrid screen, Co-IP in multiple cell lines, and deletion-mutant domain mapping

    PMID:20544796

    Open questions at the time
    • Functional consequence of EDD and PABP binding not established
    • No demonstration that these interactions affect specific mRNA translation
  10. 2011 High

    Resolved the structural basis of PP2Ac protection: a crystallized TPR-like N-terminal domain with an open PP2Ac-binding helix and embedded UIM, plus the C-terminal Mid1-binding domain, are both required to shield PP2Ac from degradation.

    Evidence X-ray crystallography, DEER spectroscopy, cycloheximide chase, tandem ubiquitin-binding precipitation, and mutagenesis

    PMID:21454489

    Open questions at the time
    • Full-length IGBP1-PP2Ac-Mid1 complex structure not determined
    • Conformational switching between protection and degradation not captured
  11. 2011 High

    Linked IGBP1 to oncogenic transformation and its regulation: elevated IGBP1 lowers PP2A activity, promotes proliferation/survival and tumor formation, and is repressed by miR-34b targeting its 3'-UTR.

    Evidence Overexpression xenografts, siRNA knockdown, PP2A activity assays, and miR-34b luciferase reporter validation

    PMID:21339737

    Open questions at the time
    • How elevated IGBP1 selectively reduces PP2A activity not mechanistically dissected
    • Driver vs passenger status in primary tumors not established
  12. 2011 Medium

    Identified a ligand that converts IGBP1 to a proapoptotic node: lactoferrin binding to IGBP1 reduces PP2A activity and triggers apoptosis in lung adenocarcinoma cells.

    Evidence Protein microarray, Co-IP, immunofluorescence, PP2A activity assay, and caspase-3/APAF-1 analysis

    PMID:21378334

    Open questions at the time
    • Single cell line and single lab
    • Structural basis of lactoferrin-IGBP1 binding and its effect on PP2Ac not defined
  13. 2017 Medium

    Extended miRNA control: miR-3941 and miR-34b directly target the IGBP1 3'-UTR to suppress its expression and induce apoptosis, reinforcing IGBP1 as a survival factor in lung adenocarcinoma.

    Evidence miRNA array, TargetScan prediction, 3'-UTR luciferase reporter, and miRNA transfection with proliferation/apoptosis readouts

    PMID:28012229

    Open questions at the time
    • In vivo relevance of these miRNA-IGBP1 axes not tested
    • Downstream survival effectors not identified in this study
  14. 2018 High

    Revealed a non-PP2A-centric output in epithelium: IGBP1 stabilizes the RNA-binding protein HuR by preventing IKKα-mediated phosphorylation and degradation, maintaining junction proteins and intestinal barrier function.

    Evidence Intestinal epithelial cell-specific knockout mice, siRNA, HuR overexpression rescue, IKKα phosphorylation and barrier assays

    PMID:29555726

    Open questions at the time
    • How IGBP1 restrains IKKα-mediated HuR phosphorylation mechanistically unclear
    • Whether PP2A activity is involved in HuR stabilization not resolved
  15. 2022 High

    Defined a stimulus-regulated 'PP2A switch': an IGBP1-PP2Ac dimer dephosphorylates inhibitory pSer608-p85 to sustain PI3K/AKT activity in resting cells, then upon GqPCR activation shifts to AKT to drive its dephosphorylation and JNK-dependent apoptosis.

    Evidence Reciprocal Co-IP, proximity ligation, kinase/phosphatase activity assays, and TUNEL/PARP1 apoptosis readouts

    PMID:34998390

    Open questions at the time
    • Signal that triggers the IGBP1-PP2Ac relocation from PI3K to AKT not identified
    • Generality across receptor types not established
  16. 2022 High

    Established a metabolic role: IGBP1 maintains adipocyte insulin signaling by associating with YBX1 to suppress PTP1B, sustaining insulin receptor phosphorylation, adipogenesis, and systemic insulin sensitivity.

    Evidence Adipocyte-specific knockout mice, Co-IP of IGBP1-YBX1, PTP1B and insulin receptor phosphorylation analysis, and metabolic phenotyping

    PMID:36241662

    Open questions at the time
    • Mechanism by which IGBP1-YBX1 represses PTP1B expression not defined
    • Relative contributions of PP2A stabilization vs YBX1 axis not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IGBP1 dictates PP2Ac substrate selectivity and orchestrates its switching between distinct effector complexes (PI3K, AKT, mTOR-STAT1, c-Jun/p53) across tissues remains unresolved.
  • No unified model of how one IGBP1-PP2Ac dimer selects context-specific substrates
  • Upstream signals controlling complex reassignment largely undefined
  • No full-length structural model of IGBP1 in any effector complex

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 2
Partners
AKTEDDMID1PABPPIK3R1PP2ACSTAT1YBX1
Complex memberships
IGBP1-PP2Ac dimermTOR-STAT1-IGBP1-PP2Ac complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Alpha4 (IGBP1), a noncatalytic subunit of PP2A, is required to repress apoptosis in murine cells. Alpha4 deletion leads to increased dephosphorylation of transcription factors c-Jun and p53, transcription of multiple proapoptotic genes, and cell death that is suppressible by blocking protein synthesis or overexpressing Bcl-xL. Conditional gene deletion (alpha4 knockout) in murine cells, epistasis with Bcl-xL overexpression and translation inhibitors, transcriptional profiling Science High 15499020
2010 Alpha4 (IGBP1) contains a novel ubiquitin-interacting motif (UIM, residues 46–60) that allows alpha4 to bind ubiquitin and act as an adaptor bridging PP2Ac and the E3 ubiquitin ligase Mid1. The UIM within alpha4 suppresses polyubiquitination of PP2Ac; deletion of the UIM enhances PP2Ac polyubiquitination. NMR analysis of alpha4–ubiquitin interaction; co-immunoprecipitation of alpha4, PP2Ac, and Mid1; UIM deletion mutants with ubiquitination assays Biochemistry High 20092282
2011 Both the C-terminal Mid1-binding domain and the N-terminal PP2Ac-binding domain of Alpha4 are required for Alpha4-mediated protection of PP2Ac from polyubiquitination and degradation. X-ray crystallography of the N-terminal domain showed a flexible TPR-like fold with a PP2Ac-binding helix in a more open conformation than yeast Tap42, and an embedded UIM. X-ray crystallography of Alpha4 N-terminal domain; double electron-electron resonance (DEER) spectroscopy; cycloheximide chase assays; tandem ubiquitin-binding entity precipitations; site-directed mutagenesis The Journal of biological chemistry High 21454489
2007 Alpha4 (IGBP1) promotes cell spreading and migration through activation of Rac1 GTPase. Fibroblasts lacking alpha4 show reduced Rac1-GTP levels and impaired spreading/migration; constitutively active Rac1 rescues the alpha4-null defects; inhibition of Rac1 blocks alpha4-promoted migration. T cell-specific alpha4 transgenic mice display increased lymphocyte motility and chemotaxis. Alpha4 conditional knockout fibroblasts; alpha4 overexpression; constitutively active Rac1 rescue; Rac1 GTPase pull-down assays; T cell-specific transgenic mice with chemotaxis assays The Journal of biological chemistry High 17693407
2008 Igbp1 (alpha4) mRNA is selectively recruited to polysomes downstream of SCF-induced PI3K activation in erythroblasts. Constitutive Igbp1 expression impairs erythroid differentiation, sustains 4EBP and p70S6k phosphorylation, and enhances polysome recruitment of multiple eIF4E-sensitive mRNAs, establishing a positive feedback loop on translation initiation that maintains PP2A/mTOR signaling. Polysome fractionation with microarray comparison; PI3K inhibitor treatments; eIF4E overexpression; retroviral constitutive Igbp1 expression with erythroid differentiation assays and phosphorylation analysis Blood High 18625885
2009 Alpha4 (IGBP1), together with PP2Ac, forms a macromolecular complex with mTOR and STAT1. Inactivation of mTOR enhances alpha4 association with the complex and increases STAT1 nuclear content in a PP2Ac-dependent manner. Depletion of alpha4 enhances STAT1-dependent gene expression (IRF-1, caspase-1, hiNOS, Fas), independently of p70 S6K and Akt. Co-immunoprecipitation of mTOR-STAT1-alpha4-PP2Ac complex; siRNA depletion of alpha4, PP2A, or mTOR; nuclear fractionation; gene expression analysis The Journal of biological chemistry Medium 19553685
2010 Alpha4 (IGBP1) interacts physically with EDD E3 ubiquitin ligase (at its C-terminal region, independent of the PP2Ac-binding site) and with poly(A)-binding protein (PABP) in multiple cell lines, suggesting involvement in translation initiation steps downstream of mTOR. Yeast two-hybrid screening; co-immunoprecipitation of alpha4 with EDD and PABP; alpha4 deletion mutant mapping of EDD-binding site Journal of cellular biochemistry Medium 20544796
2003 T cell-specific deletion of alpha4 (IGBP1) severely arrests T cell development at the CD4/CD8 double-negative 3 stage due to decreased cell proliferation (not increased apoptosis). Alpha4-deficient thymocytes show impaired proliferative responses to anti-CD3 stimulation, IL-2, IL-1, and TNF, and severely reduced CD3-induced CD25 expression. Cre/loxP T cell-specific gene deletion (Lck-alpha4– mice); flow cytometry analysis of T cell subsets; proliferation assays; apoptosis assays European journal of immunology High 12811850
1997 Human alpha4 (IGBP1) gene is located at Xq13.1–q13.3, is expressed ubiquitously as a 1.4-kb mRNA in immune and other tissues, and encodes a 45-kDa protein structurally related to yeast TAP42, a component of the rapamycin-sensitive signaling pathway. Genomic cloning; Northern blotting; anti-human alpha4 antibody detection of ~45-kDa protein; sequence alignment with TAP42 Genomics Medium 9441740
2006 Human alpha4 (IgBP1) and yeast Tap42 adopt elongated shapes in solution (Rg ~41–43 Å, Dmax ~142–147 Å) as determined by small-angle X-ray scattering. The N-terminal domain alone (deletion mutants alpha4Δ222 and alpha4Δ236) is globular, highly stable, and predominantly α-helical, while the C-terminal region is less structured and more susceptible to proteolysis. Small-angle X-ray scattering (SAXS); circular dichroism; thermal unfolding kinetics; recombinant truncation mutants expressed in E. coli Biochimica et biophysica acta Medium 16517231
2011 Alpha4 (IGBP1) is highly expressed in carcinogen-transformed human cells and primary human cancers. Elevated alpha4 increases cell proliferation, promotes survival, decreases PP2A-attributable phosphatase activity, and enables non-transformed cells to form tumors in immunodeficient mice. MiR-34b suppresses alpha4 expression by targeting its 3′-UTR. Alpha4 overexpression in HEK293/L02R cells with xenograft tumor formation; siRNA knockdown; PP2A activity assay; luciferase reporter for miR-34b target validation Oncogene High 21339737
2011 Binding of lactoferrin to IGBP1 reduces PP2A catalytic activity and triggers apoptosis in PC-14 lung adenocarcinoma cells. The lactoferrin-IGBP1 complex was confirmed by protein microarray screening, co-immunoprecipitation, and immunofluorescence. Protein microarray with lactoferrin as probe; co-immunoprecipitation; immunofluorescence co-localization; PP2A phosphatase activity assay; caspase-3/APAF-1 expression analysis Anticancer research Medium 21378334
2017 MiR-3941 (and miR-34b) suppress IGBP1 expression by directly targeting the 3′-UTR of IGBP1 mRNA. Transfection of either miRNA into lung adenocarcinoma cell lines suppresses IGBP1 protein expression, reduces cell proliferation, and induces apoptosis comparable to siIGBP1. MiRNA array; in silico TargetScan analysis; 3′-UTR luciferase reporter assay; miRNA transfection with IGBP1 protein/mRNA quantification; proliferation and apoptosis assays Cancer science Medium 28012229
2018 Alpha4 (IGBP1) controls intestinal epithelial homeostasis by stabilizing the RNA-binding protein HuR. Alpha4 silencing leads to IκB kinase α-mediated phosphorylation of HuR, triggering ubiquitin-mediated HuR proteolysis, which in turn reduces intercellular junction proteins and disrupts epithelial barrier function. Ectopic HuR expression in alpha4-deficient cells rescues junction proteins and barrier function. Intestinal epithelial cell-specific alpha4 conditional KO mice; siRNA knockdown in cultured IECs; HuR overexpression rescue; IκBKα phosphorylation assays; barrier function assays; immunofluorescence of junction proteins Molecular and cellular biology High 29555726
2022 IGBP1 mediates a 'PP2A switch' in GqPCR signaling: in resting cells, an IGBP1-PP2Ac dimer binds PI3K and dephosphorylates inhibitory pSer608-p85, maintaining high PI3K/AKT activity. Upon GqPCR activation, the IGBP1-PP2Ac dimer detaches from PI3K and instead associates with AKT together with PP2Aa, causing AKT dephosphorylation and inactivation that leads to JNK-dependent apoptosis. Co-immunoprecipitation of IGBP1-PP2Ac-PI3K and IGBP1-PP2Ac-AKT complexes; proximity ligation assay; kinase/phosphatase activity assays; TUNEL and PARP1 cleavage for apoptosis; phospho-specific antibodies for pSer608-p85 and pAKT Cell communication and signaling High 34998390
2022 Alpha4 (IGBP1) maintains insulin signaling in adipocytes by associating with Y-box protein 1 (YBX1), which suppresses PTP1B expression. Loss of alpha4 in adipocytes reduces α4-YBX1 association, elevates PTP1B, reduces insulin receptor tyrosine phosphorylation, and decreases PP2A levels, resulting in impaired Akt-mediated signaling, defective adipogenesis, altered mitochondrial oxidation, and systemic insulin resistance. Adipocyte-specific alpha4 knockout mice; co-immunoprecipitation of alpha4 with YBX1; PTP1B expression analysis; insulin receptor phosphorylation assays; metabolic phenotyping including thermogenesis and hepatosteatosis Nature communications High 36241662

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature 462 9582073
1999 Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature 277 10604475
2005 Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale. Neurology 250 15851719
2002 GABA(A) receptor changes in delta subunit-deficient mice: altered expression of alpha4 and gamma2 subunits in the forebrain. The Journal of comparative neurology 195 11932935
2007 Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation 187 17646580
2007 Neurosteroid regulation of GABA(A) receptors: Focus on the alpha4 and delta subunits. Pharmacology & therapeutics 179 17512983
2006 Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors. Molecular pharmacology 167 17132685
2010 Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors: role of alpha4 and alpha7 receptors in neuroprotection. Journal of molecular neuroscience : MN 163 19714494
2008 Three novel collagen VI chains, alpha4(VI), alpha5(VI), and alpha6(VI). The Journal of biological chemistry 149 18400749
2004 Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis. Blood 136 15138161
1998 GFR alpha-4 and the tyrosine kinase Ret form a functional receptor complex for persephin. Current biology : CB 132 9740802
2004 The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis. Science (New York, N.Y.) 129 15499020
2002 Alpha4 integrins and the immune response. Immunological reviews 125 12234367
2008 Natalizumab: targeting alpha4-integrins in multiple sclerosis. Neuro-degenerative diseases 123 18075270
2010 Na,K-ATPase alpha4 isoform is essential for sperm fertility. Proceedings of the National Academy of Sciences of the United States of America 121 21187400
2006 Contribution of alpha6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with alpha4 integrins. Blood 103 16439681
1998 Nicotinic receptor subtypes in the developing chick brain: appearance of a species containing the alpha4, beta2, and alpha5 gene products. Molecular pharmacology 93 9495803
2011 EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. The Journal of cell biology 87 21949412
2002 Localization of laminin alpha4-chain in developing and adult human tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 85 12133914
1997 Primary structure, developmental expression, and immunolocalization of the murine laminin alpha4 chain. The Journal of biological chemistry 75 9346933
2005 Integrin alpha4beta1 promotes focal adhesion kinase-independent cell motility via alpha4 cytoplasmic domain-specific activation of c-Src. Molecular and cellular biology 74 16227616
2014 Role of integrin alpha4 in drug resistance of leukemia. Frontiers in oncology 73 24904821
2013 How natalizumab binds and antagonizes α4 integrins. The Journal of biological chemistry 73 24047894
2019 Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins. Immunity 72 30650373
2003 Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin. The American journal of gastroenterology 72 14638336
1999 Developmental expression and cellular origin of the laminin alpha2, alpha4, and alpha5 chains in the intestine. Developmental biology 72 10364433
2017 PI3Kγ Activates Integrin α4 and Promotes Immune Suppressive Myeloid Cell Polarization during Tumor Progression. Cancer immunology research 70 28963139
2005 Cardiomyopathy associated with microcirculation dysfunction in laminin alpha4 chain-deficient mice. The Journal of biological chemistry 69 16204254
2007 Alpha4 integrins are type I cAMP-dependent protein kinase-anchoring proteins. Nature cell biology 66 17369818
2008 Guanylate binding protein-1 inhibits spreading and migration of endothelial cells through induction of integrin alpha4 expression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 64 18697840
1992 Contiguous localization of the genes encoding human insulin-like growth factor binding proteins 1 (IGBP1) and 3 (IGBP3) on chromosome 7. Genomics 62 1373120
2010 Alpha4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination. Biochemistry 60 20092282
2008 CCL25 and CCL28 promote alpha4 beta7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow. American journal of physiology. Gastrointestinal and liver physiology 60 18308860
1998 The interrelationship of alpha4 integrin and matrix metalloproteinase-2 in the pathogenesis of experimental autoimmune encephalomyelitis. Laboratory investigation; a journal of technical methods and pathology 60 9840619
1998 Expression of laminin alpha3, alpha4, and alpha5 chains by alveolar epithelial cells and fibroblasts. American journal of respiratory cell and molecular biology 58 9698595
2014 The membrane scaffold CD82 regulates cell adhesion by altering α4 integrin stability and molecular density. Molecular biology of the cell 57 24623721
2009 Alpha4-containing GABAA receptors in the nucleus accumbens mediate moderate intake of alcohol. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 19144854
2008 The differential amino acid requirement within osteopontin in alpha4 and alpha9 integrin-mediated cell binding and migration. Matrix biology : journal of the International Society for Matrix Biology 57 19000758
2012 Progenitor cell mobilization and recruitment: SDF-1, CXCR4, α4-integrin, and c-kit. Progress in molecular biology and translational science 56 22917234
2014 Therapeutic uses of anti-α4-integrin (anti-VLA-4) antibodies in multiple sclerosis. International immunology 53 25326459
2015 Laminin α4 (LAMA4) expression promotes trophoblast cell invasion, migration, and angiogenesis, and is lowered in preeclamptic placentas. Placenta 50 26059342
2008 Motility-related actinin alpha-4 is associated with advanced and metastatic ovarian carcinoma. Laboratory investigation; a journal of technical methods and pathology 50 18362906
2006 Glypican-1 and alpha4(V) collagen are required for Schwann cell myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 16407548
2008 alpha4-Integrin antagonism with natalizumab: effects and adverse effects. Journal of neurology 47 19300961
2004 Aberrant methylation of integrin alpha4 gene in human gastric cancer cells. Oncogene 47 14990990
2006 Immunolabeling demonstrates the interdependence of mouse brain alpha4 and beta2 nicotinic acetylcholine receptor subunit expression. The Journal of comparative neurology 45 17072836
2012 Characteristics of concatemeric GABA(A) receptors containing α4/δ subunits expressed in Xenopus oocytes. British journal of pharmacology 44 21950777
2011 The E3 ubiquitin ligase- and protein phosphatase 2A (PP2A)-binding domains of the Alpha4 protein are both required for Alpha4 to inhibit PP2A degradation. The Journal of biological chemistry 43 21454489
2009 Inactivation of mammalian target of rapamycin increases STAT1 nuclear content and transcriptional activity in alpha4- and protein phosphatase 2A-dependent fashion. The Journal of biological chemistry 43 19553685
2004 The alpha4 laminin subunit regulates endothelial cell survival. Experimental cell research 43 14980521
2001 Identification of a new mutation in the alpha4(IV) collagen gene in a family with autosomal dominant Alport syndrome and hypercholesterolaemia. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 43 11572889
2007 The PP2A-associated protein alpha4 plays a critical role in the regulation of cell spreading and migration. The Journal of biological chemistry 40 17693407
2011 α4 is highly expressed in carcinogen-transformed human cells and primary human cancers. Oncogene 39 21339737
2007 GABAA receptors in the thalamus: alpha4 subunit expression and alcohol sensitivity. Alcohol (Fayetteville, N.Y.) 38 17521848
2008 Igbp1 is part of a positive feedback loop in stem cell factor-dependent, selective mRNA translation initiation inhibiting erythroid differentiation. Blood 35 18625885
2008 NG2, a novel proapoptotic receptor, opposes integrin alpha4 to mediate anoikis through PKCalpha-dependent suppression of FAK phosphorylation. Cell death and differentiation 33 18292781
2022 Lymph node fibroblastic reticular cells preserve a tolerogenic niche in allograft transplantation through laminin α4. The Journal of clinical investigation 31 35775481
2004 Transcriptional regulation of the mouse gene encoding the alpha-4 subunit of the GABAA receptor. The Journal of biological chemistry 31 15265862
2016 Phenol-soluble modulin α4 mediates Staphylococcus aureus-associated vascular leakage by stimulating heparin-binding protein release from neutrophils. Scientific reports 30 27383625
2017 α4-integrin receptor desaturation and disease activity return after natalizumab cessation. Neurology(R) neuroimmunology & neuroinflammation 29 28856176
2015 Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus. Journal of neurochemistry 28 25708312
2015 Differential α4(+)/(-)β2 Agonist-binding Site Contributions to α4β2 Nicotinic Acetylcholine Receptor Function within and between Isoforms. The Journal of biological chemistry 28 26644472
2014 Hepatic farnesoid X-receptor isoforms α2 and α4 differentially modulate bile salt and lipoprotein metabolism in mice. PloS one 28 25506828
2007 Alpha4 chain laminins are widely expressed in renal cell carcinomas and have a de-adhesive function. Laboratory investigation; a journal of technical methods and pathology 28 17533363
2006 New approaches to blockade of alpha4-integrins, proven therapeutic targets in chronic inflammation. Biochemical pharmacology 27 16870156
2007 Postnatal upregulation of alpha4 and alpha3 nicotinic receptor subunits in the brain of alpha7 nicotinic receptor-deficient mice. Neuroscience 26 17434683
2000 Alpha4 integrins in cardiovascular development and diseases. Trends in cardiovascular medicine 26 11282303
2019 Laminin α2, α4, and α5 Chains Positively Regulate Migration and Survival of Oligodendrocyte Precursor Cells. Scientific reports 25 31882770
2011 Binding of lactoferrin to IGBP1 triggers apoptosis in a lung adenocarcinoma cell line. Anticancer research 25 21378334
2019 Regulation of cell migration by α4 and α9 integrins. The Biochemical journal 24 30819933
2016 Integrin α4-positive human trophoblast progenitors: functional characterization and transcriptional regulation. Human reproduction (Oxford, England) 23 27083540
2004 Expression of alphav, alpha4, alpha5 and beta3 integrin subunits, fibronectin and vitronectin in goat peri-implantation. Animal reproduction science 23 15036518
1997 Expression and chromosomal localization of the human alpha 4/IGBP1 gene, the structure of which is closely related to the yeast TAP42 protein of the rapamycin-sensitive signal transduction pathway. Genomics 23 9441740
2018 α4 Coordinates Small Intestinal Epithelium Homeostasis by Regulating Stability of HuR. Molecular and cellular biology 22 29555726
2018 Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype. Clinical immunology (Orlando, Fla.) 22 29842945
2017 miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma. Cancer science 22 28012229
2014 Monoclonal antibodies to human laminin α4 chain globular domain inhibit tumor cell adhesion and migration on laminins 411 and 421, and binding of α6β1 integrin and MCAM to α4-laminins. Matrix biology : journal of the International Society for Matrix Biology 22 24681327
2012 Dynamic alterations in integrin α4 expression by hypoxia are involved in trophoblast invasion during early implantation. Journal of cellular biochemistry 22 21976114
2017 The (α4)3(β2)2 Stoichiometry of the Nicotinic Acetylcholine Receptor Predominates in the Rat Motor Cortex. Molecular pharmacology 21 28698187
2015 The Role of Laminin α4 in Human Umbilical Vein Endothelial Cells and Pathological Mechanism of Preeclampsia. Reproductive sciences (Thousand Oaks, Calif.) 21 25676580
2016 Effects of varenicline on alpha4-containing nicotinic acetylcholine receptor expression and cognitive performance in mice. Neuropharmacology 20 27012889
2012 Integrins α4 and αM, collagen1A1, and matrix metalloproteinase 7 are upregulated in acute Kawasaki disease vasculopathy. Pediatric research 20 23344661
2010 alpha4 phosphoprotein interacts with EDD E3 ubiquitin ligase and poly(A)-binding protein. Journal of cellular biochemistry 20 20544796
2022 Arginine Methylation of Integrin Alpha-4 Prevents Fibrosis Development in Alcohol-Associated Liver Disease. Cellular and molecular gastroenterology and hepatology 18 36191854
2019 Laminin α4 contributes to airway remodeling and inflammation in asthma. American journal of physiology. Lung cellular and molecular physiology 18 31553662
2023 Astrocytic α4-containing nAChR signaling in the hippocampus governs the formation of temporal association memory. Cell reports 17 37352098
2019 FAK inhibition reduces metastasis of α4 integrin-expressing melanoma to lymph nodes by targeting lymphatic VCAM-1 expression. Biochemical and biophysical research communications 17 30660359
2011 The wake-promoting transmitter histamine preferentially enhances α-4 subunit-containing GABAA receptors. Neuropharmacology 17 21640733
2010 Liprin-α4 is a new hypoxia-inducible target gene required for maintenance of cell-cell contacts. Experimental cell research 17 20599943
2006 The role of the alpha4 integrin-paxillin interaction in regulating leukocyte trafficking. Experimental & molecular medicine 17 16819276
1998 Promoter analysis of the neuronal nicotinic acetylcholine receptor alpha4 gene: methylation and expression of the transgene. The European journal of neuroscience 17 9749753
2016 Ethanol Regulation of Synaptic GABAA α4 Receptors Is Prevented by Protein Kinase A Activation. The Journal of pharmacology and experimental therapeutics 16 26857960
2011 SWAP-70 regulates erythropoiesis by controlling α4 integrin. Haematologica 16 21880631
2009 Aberrant DNA methylation of integrin alpha4: a potential novel role for metastasis of cholangiocarcinoma. Journal of cancer research and clinical oncology 16 19655168
2022 GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch. Cell communication and signaling : CCS 15 34998390
2022 Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling. Nature communications 15 36241662
2020 SOD3 boosts T cell infiltration by normalizing the tumor endothelium and inducing laminin-α4. Oncoimmunology 15 32934887
2006 Low resolution structure of the human alpha4 protein (IgBP1) and studies on the stability of alpha4 and of its yeast ortholog Tap42. Biochimica et biophysica acta 15 16517231
2005 Biochemical characterization of Silene alba alpha4-fucosyltransferase and Lewis a products. Glycoconjugate journal 15 15864437
2003 T cell-specific gene targeting reveals that alpha4 is required for early T cell development. European journal of immunology 15 12811850

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