Affinage

LIMS1

LIM and senescent cell antigen-like-containing domain protein 1 · UniProt P48059

Length
325 aa
Mass
37.3 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LIMS1 (PINCH-1) is a LIM-domain-only adaptor that nucleates assembly of the ILK–PINCH–parvin (IPP) complex at integrin cell–matrix adhesions, coupling extracellular matrix engagement to intracellular survival, spreading, and migration signaling (PMID:10022929, PMID:12432066, PMID:14551191). Its N-terminal LIM1 domain binds the ankyrin-repeat domain of ILK as a high-affinity 1:1 complex (Kd ~68 nM), a recognition event resolved at atomic resolution by NMR and crystallography in which five stacked ILK ankyrin repeats grip the two LIM1 zinc fingers, and this interaction is required for focal-adhesion targeting of both partners and for the mutual proteasome-dependent stabilization of PINCH-1, ILK, and parvin (PMID:11078733, PMID:19074270, PMID:19117955, PMID:10022929, PMID:14551191). Beyond ILK, LIMS1 acts as a multivalent hub: its LIM4 domain engages the third SH3 domain of Nck2 to link integrin signaling to growth-factor and small-GTPase pathways, and its C-terminal/LIM5 region binds RSU-1, which stabilizes the complex and restrains JNK signaling while its leucine-rich-repeat solenoid blocks IPP-mediated F-actin bundling (PMID:10022929, PMID:9843575, PMID:12794636, PMID:15596544, PMID:15878342, PMID:33587032). Functionally, LIMS1 sustains pro-survival signaling—maintaining Akt/PKB phosphorylation in part by directly binding and inhibiting PP1α, and suppressing Bim-driven apoptosis through ERK-dependent Bim turnover (PMID:20530873, PMID:18063582, PMID:21670146). Genetic loss in mouse, Drosophila, C. elegans, and zebrafish establishes essential, partly ILK-independent roles in adhesion-complex assembly, epithelial polarity, cell survival, and cardiac function (PMID:15976450, PMID:12736206, PMID:17662976, PMID:21670146). LIMS1 additionally controls partner protein stability and stress responses by inhibiting Smurf1-mediated ubiquitination of BMPR2 to augment BMP signaling under ECM stiffening, regulating myoferlin degradation in breast cancer, and limiting DRP1-driven mitochondrial fragmentation to support proline biosynthesis and tumor growth (PMID:31578224, PMID:31801973, PMID:33004813).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Established the founding molecular interaction—that PINCH directly binds ILK—defining LIMS1 as an ILK partner and seeding the adhesion-adaptor model.

    Evidence Yeast two-hybrid, solid-phase binding, and Co-IP mapping LIM1 to the ILK ankyrin domain, plus identification of a ternary ILK–PINCH–Nck2 complex

    PMID:10022929 PMID:9843575

    Open questions at the time
    • Did not establish the structural basis or affinity of the interaction
    • Functional consequence at adhesions not yet defined
  2. 2001 Medium

    Showed the PINCH–ILK interaction is functionally required for adhesion-site targeting and that disrupting it impairs cell spreading and motility, converting a binding event into a cell-behavior phenotype.

    Evidence Dominant-negative LIM1/ankyrin fragment overexpression with immunofluorescence and spreading/motility assays

    PMID:10574708 PMID:11694512

    Open questions at the time
    • Dominant-negative approach does not exclude off-pathway effects
    • Downstream signaling not resolved
  3. 2003 High

    Resolved structural rules of LIMS1 recognition and demonstrated organism-level requirement, showing LIM1 folds as tandem zinc fingers binding ILK and that PINCH loss disrupts integrin-dependent adhesion across species.

    Evidence NMR of LIM1 and LIM4 interfaces; Drosophila, C. elegans, and Schwann cell genetic and cell-biological analyses

    PMID:11078733 PMID:12528177 PMID:12736206 PMID:12794636 PMID:17662976

    Open questions at the time
    • Atomic detail of the LIM1–ILK complex still pending crystallography
    • Nuclear shuttling function unresolved at this stage
  4. 2003 High

    Defined the IPP complex as a mutually stabilizing unit whose assembly precedes adhesion and sustains Akt/PKB phosphorylation, linking LIMS1 to survival signaling.

    Evidence Structure-based mutagenesis, siRNA knockdown, phosphorylation immunoblots, and proteasome-inhibitor experiments

    PMID:12432066 PMID:14551191

    Open questions at the time
    • Direct enzymatic basis of Akt regulation not yet identified
    • Mechanism of complex degradation not defined
  5. 2005 High

    Dissected LIMS1 into separable functional modules and identified RSU-1 as a LIM5-binding partner restraining JNK, revealing the adaptor's combinatorial signaling logic.

    Evidence Domain deletion/mutagenesis with functional readouts, yeast two-hybrid/GST pulldown, RNAi, and mouse knockout developmental analysis

    PMID:15596544 PMID:15798193 PMID:15878342 PMID:15941716 PMID:15976450

    Open questions at the time
    • ILK-independent embryonic functions mechanistically unexplained
    • How RSU-1 antagonizes JNK biochemically unresolved
  6. 2007 High

    Connected LIMS1 to apoptosis control by showing it suppresses Bim through ERK-dependent phosphorylation and turnover, with Bim depletion fully rescuing PINCH-loss death.

    Evidence RNAi knockdown, phosphorylation assays, Bim siRNA rescue, and subcellular fractionation

    PMID:17656471 PMID:18063582

    Open questions at the time
    • Upstream link from LIMS1 to Src/ERK activation incomplete
    • Relative contribution of EMT vs survival in vivo unclear
  7. 2008 High

    Provided atomic-resolution structures of the ILK ankyrin–LIM1 complex and measured nanomolar affinity, explaining prior deletion data and enabling precise interface mutants.

    Evidence X-ray crystallography at 1.6 Å and solution NMR with ITC affinity (Kd ~68 nM) and localization-validated point mutants

    PMID:19074270 PMID:19117955

    Open questions at the time
    • Structure of the full IPP ternary complex not determined
    • Dynamics of assembly in vivo not captured
  8. 2010 High

    Identified a direct enzymatic mechanism for survival signaling—LIMS1 binds and inhibits PP1α to elevate Akt phosphorylation—and resolved competition between PINCH1 and PINCH2 for ILK.

    Evidence Co-IP, in vitro phosphatase assays, radioresistance assays, and PINCH2 LIM1–ILK crystal structure

    PMID:19963065 PMID:20530873

    Open questions at the time
    • Whether PP1α inhibition occurs at adhesions or elsewhere unclear
    • Physiological balance between PINCH1 and PINCH2 in tissues undefined
  9. 2011 Medium

    Extended LIMS1 function to nuclear and tissue-specific signaling, showing nuclear shuttling and WT1 repression, RSU-1 stabilization controlling JNK survival, and an essential cardiac role rescued by active Akt.

    Evidence Co-IP/GST pulldown with reporter assays, null embryoid bodies with JNK inhibition, NF-κB reporters, and zebrafish morpholino knockdown with constitutively active PKB rescue

    PMID:21343177 PMID:21390327 PMID:21670146 PMID:22946061

    Open questions at the time
    • NES/NLS signals only putatively mapped
    • Physiological trigger for nuclear translocation incompletely defined
  10. 2013 High

    Tested the genetic necessity of the PINCH–ILK bond directly, revealing it is dispensable for viability alone but synthetically lethal with RSU-1 loss, establishing RSU-1 as a compensatory module.

    Evidence Transgenic Drosophila Q38A point mutant and double-mutant genetic epistasis

    PMID:22467865

    Open questions at the time
    • Molecular basis of RSU-1 compensation not defined
    • Mammalian relevance of the synthetic interaction untested
  11. 2015 High

    Expanded the LIMS1 adhesion interactome by identifying EPLIN as a PINCH-dependent adhesion-site component required for spreading and migration.

    Evidence Proteomic interactome MS, immunofluorescence, siRNA, and conditional knockout mice

    PMID:25609703

    Open questions at the time
    • Direct vs indirect nature of the PINCH–EPLIN association not resolved
    • Domain mediating the interaction not mapped
  12. 2019 High

    Revealed LIMS1 as a mechanoresponsive controller of partner protein stability—inhibiting Smurf1 to protect BMPR2, regulating myoferlin degradation, and driving a HIF1A/AKT-mTOR feedback loop—linking ECM mechanics to differentiation and tumor metabolism.

    Evidence Co-IP, ubiquitination assays, ECM stiffness modulation, domain-specific rescue, knockout with xenograft, and pathway-inhibitor experiments

    PMID:30679163 PMID:31578224 PMID:31801973

    Open questions at the time
    • How stiffness elevates PINCH-1 levels mechanistically unclear
    • Whether these axes operate through cytoplasmic vs nuclear LIMS1 not resolved
  13. 2021 High

    Established LIMS1 control of mitochondrial dynamics and adipocyte survival, and a structural mechanism by which RSU-1 gates IPP actin-bundling activity.

    Evidence CRISPR/siRNA knockout with DRP1 and PYCR1 rescue, adipocyte-specific double KO with Caspase-8 rescue and metabolic phenotyping, and Rsu1–PINCH1 crystal structure with F-actin bundling assays

    PMID:33004813 PMID:33587032 PMID:34380695

    Open questions at the time
    • How LIMS1 represses DRP1 expression mechanistically undefined
    • Integration of actin-regulatory and survival functions of the same C-terminal region unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LIMS1 partitions and coordinates its many activities—adhesion scaffolding, nuclear transcriptional repression, partner ubiquitination control, and mitochondrial regulation—within a single cell remains unresolved.
  • No structure of the assembled IPP complex with actin
  • Mechanism switching LIMS1 between cytoplasmic and nuclear pools undefined
  • Whether reported Tau stabilization reflects a genuine direct mechanism is uncertain (single Co-IP confirmation of an MS prediction)

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2 GO:0008092 cytoskeletal protein binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3
Partners
ILKLIMA1MYOFNCK2PPP1CARSU1SMURF1WT1
Complex memberships
ILK–PINCH–parvin (IPP) complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PINCH (LIMS1) directly binds integrin-linked kinase (ILK) through its N-terminal LIM1 domain (residues 1–70) and the ankyrin (ANK) repeat domain of ILK (residues 1–163), as demonstrated by yeast two-hybrid, solid-phase binding, and immunoaffinity co-isolation from mammalian cells. Yeast two-hybrid, solid-phase binding assay, immunoaffinity chromatography (Co-IP from mammalian cells) Molecular and cellular biology High 10022929
1999 Through its interaction with PINCH via the ILK–PINCH complex, ILK forms a ternary complex with Nck-2 (an SH2/SH3 adaptor), connecting ILK/integrin signaling to growth factor receptor and small GTPase pathways. Immunoaffinity co-isolation, yeast two-hybrid Molecular and cellular biology Medium 10022929
1998 The PINCH–Nck-2 interaction is mediated specifically by the LIM4 domain of PINCH and the third SH3 domain of Nck-2, as determined by deletion-mapping in yeast two-hybrid and co-immunoprecipitation assays. Yeast two-hybrid domain mapping, Co-IP Molecular biology of the cell Medium 9843575
1999 PINCH-binding through the ANK1 repeat of ILK is required for focal adhesion localization and clustering of ILK; an ANK1-deletion mutant of ILK that cannot bind PINCH fails to localize to focal adhesions. Mutational analysis, immunofluorescence localization Journal of cell science Medium 10574708
2001 The LIM1 domain of PINCH, which mediates ILK binding, is required for targeting PINCH to cell-matrix contact sites (focal and fibrillar adhesions); inhibiting the PINCH–ILK interaction by overexpressing either PINCH LIM1 or ILK ankyrin domain fragments retards cell spreading and reduces cell motility. Dominant-negative overexpression, immunofluorescence, cell spreading and motility assays The Journal of biological chemistry Medium 11694512
2000 NMR solution structure of the PINCH LIM1 domain was solved; it contains two contiguous zinc fingers (CCHC and CCCH types), forms a 1:1 complex with the ILK ankyrin repeat domain, and chemical shift mapping identified the LIM1 surface regions important for ILK interaction. NMR spectroscopy, gel-filtration, chemical shift mapping The Journal of biological chemistry High 11078733
2002 Assembly of the PINCH–ILK–CH-ILKBP (parvin) ternary complex precedes integrin-mediated cell adhesion and spreading, and is essential for localization of each component to cell-matrix adhesion sites; binding-defective point mutants identified by 3D structure-based analysis fail to localize. Structure-based point mutagenesis, Co-IP, immunofluorescence localization, kinase inhibitor experiments Journal of cell science High 12432066
2003 NMR structure of PINCH LIM4 domain shows it recognizes the third SH3 domain of Nck2 in a manner distinct from LIM1–ILK binding; point mutations in the SH3-binding interface of LIM4 disrupt LIM–SH3 interaction and substantially impair PINCH localization to focal adhesions. NMR spectroscopy, point mutagenesis, immunofluorescence localization Nature structural biology High 12794636
2003 In Drosophila, PINCH (steamer duck/stck) is required for integrin-dependent actin organization, cell-substratum adhesion, and epithelial cell adhesion in the wing; PINCH and ILK co-immunoprecipitate in vivo and colocalize at integrin-rich muscle-attachment sites. ILK localizes appropriately in PINCH mutants, indicating PINCH loss causes integrin defects independently of ILK mislocalization. Genetic loss-of-function (EMS alleles), Co-IP, immunofluorescence in Drosophila embryos Development (Cambridge, England) High 12736206
2003 PINCH-1 and ILK are required for cell spreading, motility, and cell survival including PKB/Akt phosphorylation (both Ser473 and Thr308); PINCH-1, ILK, and alpha-parvin are mutually dependent for protein stability (but not mRNA), mediated at least partly by proteasomes. RNA interference (siRNA knockdown), phosphorylation assays (immunoblot), cell spreading and motility assays, proteasome inhibitor experiments The Journal of biological chemistry High 14551191
2004 In Drosophila dorsal closure, PINCH is required at the leading edge of migrating epithelia and antagonizes JNK signaling; RSU-1 (Ras suppressor-1) was identified as a novel PINCH binding partner that contributes to PINCH stability, and genetic epistasis shows both PINCH and RSU-1 antagonize JNK signaling during epithelial migration. Genetic epistasis (Drosophila), native co-IP of endogenous proteins, immunofluorescence The Journal of cell biology High 15596544
2005 RSU-1 binds specifically to the LIM5 domain of PINCH1 (not PINCH2, which diverges in LIM5) via RSU-1's leucine-rich repeat region; RSU-1 co-immunoprecipitates with PINCH1 and colocalizes at focal adhesions in mammalian cells; RNAi depletion of RSU-1 inhibits cell attachment and activates JNK/p38. Yeast two-hybrid domain mapping, GST pulldown, Co-IP, immunofluorescence, RNAi knockdown Experimental cell research High 15878342
2005 PINCH-1 LIM1–ILK interaction regulates ILK protein level, cell shape, and survival signaling; LIM4–Nck2 interaction regulates cell morphology and migration but not ILK level or survival; a 15-residue C-terminal tail is required for both cell shape modulation and survival, and regulates PINCH-1 localization to focal adhesions. Domain deletion/mutagenesis, RNAi, cell shape and survival assays The Journal of biological chemistry Medium 15941716
2005 PINCH1 knockout mice arrest at peri-implantation stage with abnormal epiblast polarity, impaired cavitation, and cell-cell adhesion defects in endoderm and epiblast, phenotypes not entirely recapitulated by beta1-integrin or ILK loss, indicating PINCH1 has ILK-independent functions. Conditional gene knockout (homologous recombination), embryoid body analysis, immunostaining Journal of cell science High 15976450
2005 PINCH1 deletion in mouse embryos causes lethality by E6.5 with decreased cell proliferation and excessive cell death; cardiomyocyte-specific PINCH1 deletion produces no basal phenotype, demonstrating tissue-specific dispensability. Homologous recombination knockout, histology, echocardiography Molecular and cellular biology High 15798193
2007 PINCH-1 suppresses Bim-dependent apoptosis through the ERK pathway: loss of PINCH-1 reduces activating phosphorylation of Src and ERK1/2, decreases ERK-mediated Ser69 phosphorylation of Bim (required for Bim turnover), increases Bim levels, and promotes mitochondrial Bim translocation. Depletion of Bim completely blocked PINCH-1-loss-induced apoptosis. RNAi knockdown, phosphorylation assays, Bim siRNA rescue, subcellular fractionation The Journal of biological chemistry High 18063582
2007 PINCH-1 promotes tubular epithelial-to-mesenchymal transition (EMT) by interacting with ILK; disruption of ILK/PINCH-1 interaction (by ILK ankyrin domain overexpression or ILK inhibitor) reduces fibronectin deposition, confirming the ILK-dependent mechanism. Overexpression, siRNA knockdown, dominant-negative ILK fragment, immunofluorescence, Western blot Journal of the American Society of Nephrology Medium 17656471
2008 Crystal structure of the ILK ankyrin repeat domain bound to PINCH1 LIM1 domain at 1.6-Å resolution reveals 5 ankyrin repeats in ILK forming a concave surface to grip the two zinc fingers of PINCH1 LIM1; structure explains prior deletion data and permits identification of point mutations disrupting interaction. X-ray crystallography (1.6-Å resolution), point mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 19074270
2008 Solution NMR structure of the ILK ankyrin repeat domain (ARD)–PINCH LIM1 complex (Kd ~68 nM) shows five sequentially stacked ankyrin repeats providing a large concave electrostatic surface that grips the two zinc fingers of PINCH LIM1; mutation of a hot-spot LIM1 residue (not conserved in other LIM domains) disrupts ILK binding and abolishes PINCH targeting to focal adhesions. Solution NMR structure determination, ITC/NMR affinity measurement, mutagenesis, immunofluorescence The Journal of biological chemistry High 19117955
2009 Crystal structure of PINCH2 LIM1 domain complexed with ILK ARD at 1.9-Å resolution shows PINCH1 and PINCH2 LIM1 domains directly compete for the same binding site on ILK ARD; point mutations disrupting the interface reduce PINCH2 binding in vitro and alter PINCH2 cellular localization. X-ray crystallography (1.9 Å), in vitro binding, mutagenesis, immunofluorescence Journal of structural biology High 19963065
2010 PINCH1 directly binds protein phosphatase 1alpha (PP1alpha) and inhibits its activity, resulting in increased Akt1 phosphorylation; this mechanism promotes cell survival and radioresistance. Co-IP (direct binding), in vitro phosphatase activity assay, siRNA knockdown, in vitro and in vivo radioresistance assays The Journal of clinical investigation High 20530873
2010 PINCH-1 LIM1 domain (ILK-binding) is sufficient for cell attachment but not spreading; the C-terminal region of PINCH-1 (Rsu-1-binding region) is required for cell spreading by activating Rac1, defining two separable functional modules. Domain deletion mutant expression, cell attachment and spreading assays, Rac1 activation assay (G-LISA/pull-down) Molecular biology of the cell Medium 20926685
2011 PINCH-1 and ILK sensitize cells to TNF-α-mediated NF-κB activation; thymosin β4 directly binds PINCH-1 and ILK and inhibits their sensitizing effects on NF-κB activity, blocking RelA/p65 nuclear translocation and downstream IL-8 transcription. Overexpression, siRNA, NF-κB reporter assay, ChIP, nuclear fractionation FASEB journal Medium 21343177
2011 PINCH-1 promotes Bcl-2-dependent survival signaling and inhibits JNK-mediated apoptosis in primitive endoderm cells; mechanistically, PINCH-1 stabilizes RSU-1 protein, and loss of PINCH-1 leads to reduced RSU-1 levels, sustained JNK activity, and apoptosis. Chemical JNK inhibition attenuates apoptosis but does not reduce Bax activity, indicating two independent pro-survival pathways downstream of PINCH-1. PINCH-1 null embryoid bodies, JNK chemical inhibition, immunoblot, immunofluorescence Journal of cell science Medium 22946061
2011 In zebrafish, PINCH proteins localize at sarcomeric Z-disks and costameres; knockdown of either PINCH1 or PINCH2 destabilizes ILK, abolishes stretch-responsive gene expression, reduces PKB/Akt Ser473 phosphorylation, and causes heart failure; constitutively active PKB restores cardiac function in PINCH morphants. Zebrafish morpholino knockdown, PKB constitutively active rescue, immunostaining, echocardiography Molecular and cellular biology High 21670146
2011 PINCH1 undergoes nuclear translocation in podocytes after TGF-β1 stimulation via putative NES/NLS signals at its C-terminus; nuclear PINCH1 interacts with WT1 transcription factor through PINCH1 LIM1 and WT1 C-terminal zinc-finger domain, and represses WT1-mediated podocalyxin expression. Co-IP, GST pulldown, immunofluorescence nuclear localization, luciferase reporter assay, site-directed mutagenesis of NES/NLS PloS one Medium 21390327
2013 In Drosophila, the PINCH–ILK direct physical interaction is not required for viability, wing adhesion, or muscle function; however, disrupting PINCH–ILK binding combined with RSU-1 null mutation causes synthetic lethality, revealing a compensatory role for RSU-1 in maintaining viability when PINCH–ILK binding is compromised. Transgenic flies expressing PINCH point mutant (Q38A), double-mutant genetic epistasis Journal of cell science High 22467865
2015 PINCH-1 interacts with EPLIN (epithelial protein lost in neoplasm/LIMA1) as identified by PINCH-1 interactome isolation; EPLIN localizes to integrin adhesion sites in a PINCH-1-dependent manner, and EPLIN depletion severely attenuates keratinocyte spreading and migration, demonstrating a PINCH-1/EPLIN axis in integrin adhesion. Proteomic interactome isolation (mass spectrometry), immunofluorescence in vivo and in vitro, siRNA knockdown, conditional gene knockout mice Journal of cell science High 25609703
2019 PINCH-1 interacts with Smurf1 (SMAD-specific E3 ubiquitin ligase), inhibiting Smurf1 from binding and ubiquitinating BMPR2, thereby suppressing BMPR2 degradation; ECM stiffening increases PINCH-1 levels, activating this PINCH-1–Smurf1–BMPR2 axis to augment BMP signaling and promote mesenchymal stem cell osteogenic differentiation. Co-IP, siRNA/shRNA knockdown, BMPR2 degradation assay, osteogenic differentiation assay, stiffness modulation (soft vs. stiff ECM) The Journal of cell biology High 31578224
2019 PINCH-1 interacts with myoferlin and controls myoferlin protein level by regulating its ubiquitination and proteasome-dependent degradation; re-expression of wild-type PINCH-1 but not a myoferlin-binding-defective ΔLIM2 mutant reverses PINCH-1-deficiency-induced inhibition of breast cancer progression. Co-IP, ubiquitination assay, proteasome inhibitor, PINCH-1 KO, rescue with binding-defective mutant, tumor xenograft assay Oncogene High 31801973
2019 LIMS1 (PINCH-1) promotes HIF1A protein translation by activating AKT/mTOR signaling under oxygen-glucose deprivation; HIF1 in turn transactivates LIMS1 transcription, forming a positive feedback loop; LIMS1 also enhances GLUT1 expression and membrane translocation to support glucose uptake. siRNA knockdown, AKT/mTOR pathway inhibitors, HIF1A protein translation assay, GLUT1 localization by immunofluorescence, mouse tumor xenograft with siRNA nanocarrier Clinical cancer research Medium 30679163
2020 PINCH-1 knockout increases DRP1 expression and mitochondrial fragmentation, which suppresses kindlin-2 mitochondrial translocation and interaction with PYCR1, inhibiting proline synthesis; DRP1 depletion reverses PINCH-1-deficiency-induced defects on mitochondrial dynamics and proline synthesis, defining a PINCH-1–DRP1–PYCR1 signaling axis. CRISPR/siRNA knockout, DRP1 siRNA rescue, PYCR1 overexpression rescue, mitochondrial morphology imaging, proline synthesis assay, mouse lung adenocarcinoma model Nature communications High 33004813
2021 Crystal structures of the Rsu1–PINCH1 complex show the leucine-rich repeats of Rsu1 form a solenoid that tightly binds the C-terminal region of PINCH1; this interaction blocks IPP-complex-mediated F-actin bundling by disrupting PINCH1 binding to actin, and overexpression of Rsu1 in HeLa cells impairs stress fiber formation and cell spreading. X-ray crystallography, in vitro F-actin bundling assay, cellular overexpression with stress fiber and spreading analysis eLife High 33587032
2021 PINCH loss in adipocytes accelerates apoptosis via the Bim/Caspase-8 pathway; genetic ablation of Caspase-8 in adipocytes abolishes the effects of Pinch deficiency on obesity, glucose intolerance, and fatty liver in HFD-fed mice, establishing Caspase-8 as the downstream effector of PINCH-regulated adipocyte apoptosis. Conditional gene knockout (adipocyte-specific Pinch1/2 dKO), Caspase-8 adipocyte-specific KO rescue, apoptosis assays, metabolic phenotyping Diabetes High 34380695
2003 PINCH (UNC-97) null mutation in C. elegans causes embryonic arrest with failure of myofilament lattice and attachment structures (ILK, integrin) to assemble into organized arrays; LIM1 domain of UNC-97 is required for interaction with PAT-4/ILK and for localization to cell adhesion complexes. C. elegans genetics (null allele), yeast two-hybrid, immunofluorescence Developmental biology High 17662976
2013 PINCH-1 interacts with Tau (including hyperphosphorylated Tau) and with E3 ubiquitin ligase CHIP; silencing PINCH-1 prior to hp-Tau induction results in more efficient hp-Tau clearance, suggesting PINCH-1 stabilizes hp-Tau. Mass spectrometry (interaction prediction confirmed by Co-IP), siRNA knockdown, hp-Tau clearance assay PloS one Low 23554879
2003 In Schwann cells, PINCH undergoes CRM1-dependent nuclear export (confirmed by leptomycin B treatment causing nuclear accumulation and nuclear microinjection of antibody tracking the complex to cytoplasm); ILK activity in Schwann cells is enhanced by PDGF and TNF-α, and PINCH immunoprecipitates from stimulated cells contain threonine-phosphorylated proteins. Leptomycin B treatment, nuclear microinjection, immunofluorescence, Co-IP/ILK kinase activity assay Glia Medium 12528177

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 ILK, PINCH and parvin: the tIPP of integrin signalling. Nature reviews. Molecular cell biology 571 16493410
1999 The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells. Molecular and cellular biology 252 10022929
2009 The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase! The EMBO journal 209 20033063
2003 PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. The Journal of biological chemistry 180 14551191
1998 Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways. Molecular biology of the cell 166 9843575
1999 Integrin-linked kinase is localized to cell-matrix focal adhesions but not cell-cell adhesion sites and the focal adhesion localization of integrin-linked kinase is regulated by the PINCH-binding ANK repeats. Journal of cell science 164 10574708
2002 Assembly of the PINCH-ILK-CH-ILKBP complex precedes and is essential for localization of each component to cell-matrix adhesion sites. Journal of cell science 148 12432066
2004 The PINCH-ILK-parvin complexes: assembly, functions and regulation. Biochimica et biophysica acta 123 15246679
2001 A critical role of the PINCH-integrin-linked kinase interaction in the regulation of cell shape change and migration. The Journal of biological chemistry 101 11694512
2003 Analysis of PINCH function in Drosophila demonstrates its requirement in integrin-dependent cellular processes. Development (Cambridge, England) 98 12736206
2002 Characterization of PINCH-2, a new focal adhesion protein that regulates the PINCH-1-ILK interaction, cell spreading, and migration. The Journal of biological chemistry 95 12167643
1999 Integrin-linked kinase and PINCH: partners in regulation of cell-extracellular matrix interaction and signal transduction. Journal of cell science 94 10574698
2005 PINCH1 regulates cell-matrix and cell-cell adhesions, cell polarity and cell survival during the peri-implantation stage. Journal of cell science 92 15976450
2005 PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions. Trends in cell biology 87 16084094
2017 Tubular clathrin/AP-2 lattices pinch collagen fibers to support 3D cell migration. Science (New York, N.Y.) 86 28619886
2011 Thymosin beta4 inhibits TNF-alpha-induced NF-kappaB activation, IL-8 expression, and the sensitizing effects by its partners PINCH-1 and ILK. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 86 21343177
2010 PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1alpha. The Journal of clinical investigation 85 20530873
2012 Mycobacteria and the intraphagosomal environment: take it with a pinch of salt(s)! Traffic (Copenhagen, Denmark) 84 22462580
2019 Genomic Mismatch at LIMS1 Locus and Kidney Allograft Rejection. The New England journal of medicine 83 31091373
1992 Endogenous corticotropin-releasing factor modulates feeding induced by neuropeptide Y or a tail-pinch stressor. Peptides 83 1480513
2005 PINCH1 plays an essential role in early murine embryonic development but is dispensable in ventricular cardiomyocytes. Molecular and cellular biology 81 15798193
2009 Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation. Journal of cell science 75 19435803
2004 The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1. The Journal of cell biology 74 15596544
2002 The signaling adapter protein PINCH is up-regulated in the stroma of common cancers, notably at invasive edges. Cancer 72 12216108
2005 The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein PINCH1 and participates in adhesion-related functions. Experimental cell research 70 15878342
2008 The Rsu-1-PINCH1-ILK complex is regulated by Ras activation in tumor cells. European journal of cell biology 69 18436335
2002 Regulation of fibronectin matrix deposition and cell proliferation by the PINCH-ILK-CH-ILKBP complex. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 69 12060675
2008 The structural basis of integrin-linked kinase-PINCH interactions. Proceedings of the National Academy of Sciences of the United States of America 68 19074270
2007 PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in cancer cells. The Journal of biological chemistry 66 18063582
1997 Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age. Physiology & behavior 66 9145942
2020 PINCH-1 regulates mitochondrial dynamics to promote proline synthesis and tumor growth. Nature communications 65 33004813
2002 Presteady-state analysis of a single catalytic turnover by Escherichia coli uracil-DNA glycosylase reveals a "pinch-pull-push" mechanism. The Journal of biological chemistry 60 11907039
2007 PINCH-1 promotes tubular epithelial-to-mesenchymal transition by interacting with integrin-linked kinase. Journal of the American Society of Nephrology : JASN 58 17656471
2000 Solution structure of the focal adhesion adaptor PINCH LIM1 domain and characterization of its interaction with the integrin-linked kinase ankyrin repeat domain. The Journal of biological chemistry 58 11078733
2007 Two LIM domain proteins and UNC-96 link UNC-97/pinch to myosin thick filaments in Caenorhabditis elegans muscle. Molecular biology of the cell 57 17761533
2003 Caenorhabditis elegans UNC-98, a C2H2 Zn finger protein, is a novel partner of UNC-97/PINCH in muscle adhesion complexes. Molecular biology of the cell 56 12808046
2005 Role of the integrin-linked kinase/PINCH1/alpha-parvin complex in cardiac myocyte hypertrophy. Laboratory investigation; a journal of technical methods and pathology 54 16170337
2003 Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling. Nature structural biology 54 12794636
2009 Targeted ablation of PINCH1 and PINCH2 from murine myocardium results in dilated cardiomyopathy and early postnatal lethality. Circulation 53 19652092
2019 LIMS1 Promotes Pancreatic Cancer Cell Survival under Oxygen-Glucose Deprivation Conditions by Enhancing HIF1A Protein Translation. Clinical cancer research : an official journal of the American Association for Cancer Research 50 30679163
2005 Formation and phosphorylation of the PINCH-1-integrin linked kinase-alpha-parvin complex are important for regulation of renal glomerular podocyte adhesion, architecture, and survival. Journal of the American Society of Nephrology : JASN 50 15872073
2011 Significance of thymosin β4 and implication of PINCH-1-ILK-α-parvin (PIP) complex in human dilated cardiomyopathy. PloS one 49 21625516
2006 Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas. Molecular cancer 49 17026740
2007 Pinch1 is required for normal development of cranial and cardiac neural crest-derived structures. Circulation research 42 17272814
2019 Focal adhesion proteins Pinch1 and Pinch2 regulate bone homeostasis in mice. JCI insight 41 31723057
2011 PINCH proteins regulate cardiac contractility by modulating integrin-linked kinase-protein kinase B signaling. Molecular and cellular biology 40 21670146
2020 LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice. Bone research 37 33083097
2007 UNC-97/PINCH is involved in the assembly of integrin cell adhesion complexes in Caenorhabditis elegans body wall muscle. Developmental biology 36 17662976
2005 Molecular dissection of PINCH-1 reveals a mechanism of coupling and uncoupling of cell shape modulation and survival. The Journal of biological chemistry 36 15941716
2008 Proteomics with a pinch of salt: a cyanobacterial perspective. Saline systems 35 18412952
2006 TGF-beta1 regulates the PINCH-1-integrin-linked kinase-alpha-parvin complex in glomerular cells. Journal of the American Society of Nephrology : JASN 34 17167118
2016 Signaling via PINCH: Functions, binding partners and implications in human diseases. Gene 33 27590440
2013 Role of PINCH and its partner tumor suppressor Rsu-1 in regulating liver size and tumorigenesis. PloS one 33 24058607
2011 PINCH: More than just an adaptor protein in cellular response. Journal of cellular physiology 33 20945343
2012 Effects of exogenous galanin on neuropathic pain state and change of galanin and its receptors in DRG and SDH after sciatic nerve-pinch injury in rat. PloS one 32 22624057
2003 Identification of PINCH in Schwann cells and DRG neurons: shuttling and signaling after nerve injury. Glia 32 12528177
2003 Corticotropin-releasing factor as well as opioid and dopamine are involved in tail-pinch-induced food intake of rats. Neuroscience 32 12559107
1995 Correlation between tryptophan hydroxylase activity in the brain and predisposition to pinch-induced catalepsy in mice. Pharmacology, biochemistry, and behavior 32 7617682
2008 Structural basis of focal adhesion localization of LIM-only adaptor PINCH by integrin-linked kinase. The Journal of biological chemistry 31 19117955
2013 Rsu1 contributes to regulation of cell adhesion and spreading by PINCH1-dependent and - independent mechanisms. Journal of cell communication and signaling 30 23765260
2009 Integrins mediate their unconventional, mechanical-stress-induced secretion via RhoA and PINCH in Drosophila. Journal of cell science 29 19584096
2011 How integrins control mammary epithelial differentiation: a possible role for the ILK-PINCH-Parvin complex. FEBS letters 28 21570968
2016 Measurement of Muscle Strength in Haemodialysis Patients by Pinch and Hand Grip Strength and Comparison to Lean Body Mass Measured by Multifrequency Bio-Electrical Impedance. Annals of nutrition & metabolism 27 27288418
2007 Mechanical stretch inhibits oxidized low density lipoprotein-induced apoptosis in vascular smooth muscle cells by up-regulating integrin alphavbeta3 and stablization of PINCH-1. The Journal of biological chemistry 26 17878168
2015 The focal adhesion protein PINCH-1 associates with EPLIN at integrin adhesion sites. Journal of cell science 25 25609703
2015 Ras suppressor-1 promotes apoptosis in breast cancer cells by inhibiting PINCH-1 and activating p53-upregulated-modulator of apoptosis (PUMA); verification from metastatic breast cancer human samples. Clinical & experimental metastasis 25 25647720
2012 Double-negative T cells during HIV/SIV infections: potential pinch hitters in the T-cell lineup. Current opinion in HIV and AIDS 25 22241163
2010 Evaluation of behavior and neuropeptide markers of pain in a simple, sciatic nerve-pinch pain model in rats. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 25 20490875
2002 The future of bladder control-intravesical drug delivery, a pinch of pepper, and gene therapy. Reviews in urology 24 16985646
2010 The role of the focal adhesion protein PINCH1 for the radiosensitivity of adhesion and suspension cell cultures. PloS one 23 20927395
2019 PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis. Oncogene 22 31801973
2011 PINCH1 is transcriptional regulator in podocytes that interacts with WT1 and represses podocalyxin expression. PloS one 22 21390327
2005 Up-regulation of PINCH in the stroma of oral squamous cell carcinoma predicts nodal metastasis. Oncology reports 22 16273248
1997 Comparable dose-dependent inhibition of AP-7 sensitive strychnine-induced allodynia and paw pinch-induced nociception by mexiletine in the rat. Pain 22 9313270
1989 Membrane pinch-off and reinsertion observed in living cells of Drosophila. Journal of cellular physiology 22 2808544
2021 Pinch Loss Ameliorates Obesity, Glucose Intolerance, and Fatty Liver by Modulating Adipocyte Apoptosis in Mice. Diabetes 21 34380695
2012 PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm. Journal of cell science 21 22946061
2010 The roles of two distinct regions of PINCH-1 in the regulation of cell attachment and spreading. Molecular biology of the cell 21 20926685
1989 Somatosensory input to dopamine neurones of the monkey midbrain: responses to pain pinch under anaesthesia and to active touch in behavioural context. Progress in brain research 21 2634283
2012 A crucial role for Ras suppressor-1 (RSU-1) revealed when PINCH and ILK binding is disrupted. Journal of cell science 20 22467865
1993 Involvement of mu1 and mu2 opioid receptor subtypes in tail-pinch feeding in rats. Physiology & behavior 20 8383858
2021 LIMS1 risk genotype and T cell-mediated rejection in kidney transplant recipients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 19 33909908
2015 Chelidonine suppresses migration and invasion of MDA-MB-231 cells by inhibiting formation of the integrin-linked kinase/PINCH/α-parvin complex. Molecular medicine reports 19 25890994
2013 The integrin-linked kinase-PINCH-parvin complex supports integrin αIIbβ3 activation. PloS one 19 24376884
2018 With a pinch of extra salt-Did predatory protists steal genes from their food? PLoS biology 18 29394244
2013 Orexigenic response to tail pinch: role of brain NPY(1) and corticotropin releasing factor receptors. American journal of physiology. Regulatory, integrative and comparative physiology 18 24338440
2009 Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase. Journal of structural biology 18 19963065
2020 Intestinal microbiota characteristics of mice treated with Folium senna decoction gavage combined with restraint and tail pinch stress. 3 Biotech 17 32231961
2019 A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation. The Journal of cell biology 17 31578224
2008 PINCH expression and its significance in esophageal squamous cell carcinoma. Disease markers 17 18957717
2016 Dysregulation of PINCH signaling in mesial temporal epilepsy. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 16 27838154
2005 Morphine has an antinociceptive effect through activation of the okadaic-acid-sensitive Ser/Thr protein phosphatases PP 2 A and PP5 estimated by tail-pinch test in mice. Brain research 16 16102737
2008 Novel expression of PINCH in the central nervous system and its potential as a biomarker for human immunodeficiency virus-associated neurodegeneration. Journal of neuroscience research 15 18459134
2006 A biomechanical analysis of applied pinch force during periodontal scaling. Journal of biomechanics 15 17052721
2021 Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics. eLife 14 33587032
2016 Nanoscale Ultradense Z-Pinch Formation from Laser-Irradiated Nanowire Arrays. Physical review letters 14 27472120
2013 PINCH in the cellular stress response to tau-hyperphosphorylation. PloS one 14 23554879
2015 ILKAP, ILK and PINCH1 control cell survival of p53-wildtype glioblastoma cells after irradiation. Oncotarget 13 26460618
2013 Nephrin phosphorylation regulates podocyte adhesion through the PINCH-1-ILK-α-parvin complex. BMB reports 13 23615266
2007 Pinch forces and instrument tip forces during periodontal scaling. Journal of periodontology 13 17199545

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