FERMT3

Summary

Gene Symbol: FERMT3
Description: fermitin family member 3
Alias: KIND3, MIG-2, MIG2B, UNC112C, URP2, URP2SF, fermitin family homolog 3, MIG2-like protein, UNC-112 related protein 2, kindlin 3, unc-112-related protein 2
Species: human
Products:     FERMT3

Top Publications

  1. Kuijpers T, van de Vijver E, Weterman M, de Boer M, Tool A, van den Berg T, et al. LAD-1/variant syndrome is caused by mutations in FERMT3. Blood. 2009;113:4740-6 pubmed publisher
    ..8-kb deletion in NRXN2, and a premature stop codon (p.Arg509X) in FERMT3. Two other LAD1v patients were found to carry different stop codons in FERMT3 (p.Arg573X and p...
  2. Manevich Mendelson E, Feigelson S, Pasvolsky R, Aker M, Grabovsky V, Shulman Z, et al. Loss of Kindlin-3 in LAD-III eliminates LFA-1 but not VLA-4 adhesiveness developed under shear flow conditions. Blood. 2009;114:2344-53 pubmed publisher
    ..Deletion of the putative beta(1) Kindlin-3 binding site also retained VLA-4 adhesiveness. Thus, our study provides the first evidence that Kindlin-3 is more critical to LFA-1 than to VLA-4-adhesive functions in human lymphocytes. ..
  3. Feng C, Li Y, Yau Y, Lee H, Tang X, Xue Z, et al. Kindlin-3 mediates integrin ?L?2 outside-in signaling, and it interacts with scaffold protein receptor for activated-C kinase 1 (RACK1). J Biol Chem. 2012;287:10714-26 pubmed publisher
    ..We also show that kindlin-3 co-localizes with RACK1 in polarized SKW3 cells and human T lymphoblasts. Our findings suggest that kindlin-3 plays an important role in integrin ?L?2 outside-in signaling. ..
  4. Mory A, Feigelson S, Yarali N, Kilic S, Bayhan G, Gershoni Baruch R, et al. Kindlin-3: a new gene involved in the pathogenesis of LAD-III. Blood. 2008;112:2591 pubmed publisher
  5. Siegel D, Ashton G, Penagos H, Lee J, Feiler H, Wilhelmsen K, et al. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. Am J Hum Genet. 2003;73:174-87 pubmed
    ..Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage. ..
  6. Djaafri I, Maurice P, Labas V, Vinh J, Lemesle M, Arbeille B, et al. Platelet type III collagen binding protein (TIIICBP) presents high biochemical and functional similarities with kindlin-3. Biochimie. 2012;94:416-26 pubmed publisher
  7. Bialkowska K, Ma Y, Bledzka K, Sossey Alaoui K, Izem L, Zhang X, et al. The integrin co-activator Kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell. J Biol Chem. 2010;285:18640-9 pubmed publisher
    ..Thus, the prevailing view that individual kindlins exert their functions in a cell type-specific manner must now be modified to consider distinct functions of the different family members within the same cell type. ..
  8. McDowall A, Svensson L, Stanley P, Patzak I, Chakravarty P, Howarth K, et al. Two mutations in the KINDLIN3 gene of a new leukocyte adhesion deficiency III patient reveal distinct effects on leukocyte function in vitro. Blood. 2010;115:4834-42 pubmed publisher
    ..Mutation in the KINDLIN3 (FERMT3) gene is the cause of LAD-III in patients from the Middle East, Malta, and Turkey...
  9. Moser M, Bauer M, Schmid S, Ruppert R, Schmidt S, Sixt M, et al. Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells. Nat Med. 2009;15:300-5 pubmed publisher
    ..Thus, Kindlin-3 is essential to activate the beta1, beta2 and beta3 integrin classes, and loss of Kindlin-3 function is sufficient to cause a LAD-III-like phenotype in mice. ..

More Information

Publications100

  1. Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S, et al. Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nat Med. 2009;15:306-12 pubmed publisher
    ..Instead, we identify mutations in the KINDLIN3 (official symbol FERMT3) gene specifying the KINDLIN-3 protein as the cause of LAD-III in Maltese and Turkish subjects...
  2. Weinstein E, Bourner M, Head R, Zakeri H, Bauer C, Mazzarella R. URP1: a member of a novel family of PH and FERM domain-containing membrane-associated proteins is significantly over-expressed in lung and colon carcinomas. Biochim Biophys Acta. 2003;1637:207-16 pubmed
    ..We have also isolated the full-length clones for another novel related gene, URP2 and the previously discovered MIG-2 gene...
  3. Dixit N, Kim M, Rossaint J, Yamayoshi I, Zarbock A, Simon S. Leukocyte function antigen-1, kindlin-3, and calcium flux orchestrate neutrophil recruitment during inflammation. J Immunol. 2012;189:5954-64 pubmed publisher
  4. Malinin N, Zhang L, Choi J, Ciocea A, Razorenova O, Ma Y, et al. A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nat Med. 2009;15:313-8 pubmed publisher
    ..basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene...
  5. Lai Cheong J, Parsons M, McGrath J. The role of kindlins in cell biology and relevance to human disease. Int J Biochem Cell Biol. 2010;42:595-603 pubmed publisher
    ..3), KIND2 (FERMT2; chromosome 14q22.1) and KIND3 (FERMT3; chromosome 11q13.1)...
  6. Harburger D, Bouaouina M, Calderwood D. Kindlin-1 and -2 directly bind the C-terminal region of beta integrin cytoplasmic tails and exert integrin-specific activation effects. J Biol Chem. 2009;284:11485-97 pubmed publisher
    ..We suggest that kindlins are adaptor proteins that regulate integrin activation, that kindlin expression levels determine their effects, and that kindlins may exert integrin-specific effects. ..
  7. Morrison V, Uotila L, Llort Asens M, Savinko T, Fagerholm S. Optimal T Cell Activation and B Cell Antibody Responses In Vivo Require the Interaction between Leukocyte Function-Associated Antigen-1 and Kindlin-3. J Immunol. 2015;195:105-15 pubmed publisher
  8. Nørgaard S, Deng S, Cao W, Pocock R. Distinct CED-10/Rac1 domains confer context-specific functions in development. PLoS Genet. 2018;14:e1007670 pubmed publisher
    ..Together, we reveal that specific domains and residues within Rac GTPases can confer context-dependent functions during animal development. ..
  9. Norris A, Sundararajan L, Morgan D, Roberts Z, Lundquist E. The UNC-6/Netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone filopodial protrusion via UNC-73/Trio, Rac-like GTPases and UNC-33/CRMP. Development. 2014;141:4395-405 pubmed publisher
  10. Hu Z, Huang P, Yan Y, Zhou Z, Wang J, Wu G. Hepatitis B virus X protein related lncRNA WEE2-AS1 promotes hepatocellular carcinoma proliferation and invasion. Biochem Biophys Res Commun. 2019;508:79-86 pubmed publisher
    ..Fermitin family member 3 (FERMT3) was a downstream target of WEE2-AS1...
  11. Yates L, Füzéry A, Bonet R, Campbell I, Gilbert R. Biophysical analysis of Kindlin-3 reveals an elongated conformation and maps integrin binding to the membrane-distal β-subunit NPXY motif. J Biol Chem. 2012;287:37715-31 pubmed publisher
    ..Overall these data support current biological, clinical, and mutational data on Kindlin-3/β-tail binding and provide novel insights into the overall conformation and interactions of Kindlin-3. ..
  12. Tian D, Diao M, Jiang Y, Sun L, Zhang Y, Chen Z, et al. Anillin Regulates Neuronal Migration and Neurite Growth by Linking RhoG to the Actin Cytoskeleton. Curr Biol. 2015;25:1135-45 pubmed publisher
    ..Our results reveal a novel pathway in which Anillin transduces the RhoG signal to the actin cytoskeleton during neuronal migration and neurite growth. ..
  13. Sabino F, Hermes O, Egli F, Kockmann T, Schlage P, Croizat P, et al. In vivo assessment of protease dynamics in cutaneous wound healing by degradomics analysis of porcine wound exudates. Mol Cell Proteomics. 2015;14:354-70 pubmed publisher
    ..The data have been deposited to the ProteomeXchange Consortium with identifier PXD001198. ..
  14. Ali R, Khan A. Tracing the evolution of FERM domain of Kindlins. Mol Phylogenet Evol. 2014;80:193-204 pubmed publisher
    ..This study helps in developing a better understanding of evolutionary history of FERM domain of FDCPs and the role of FERM domain in metazoan evolution. ..
  15. Wang Z, Chi Q, Sherwood D. MIG-10 (lamellipodin) has netrin-independent functions and is a FOS-1A transcriptional target during anchor cell invasion in C. elegans. Development. 2014;141:1342-53 pubmed publisher
    ..These studies indicate that MIG-10 has distinct functions from UNC-40 signaling in cell invasion, and demonstrate that integrin coordinates invasion by localizing these molecules to the cell-basement membrane interface. ..
  16. Boras M, Volmering S, Bokemeyer A, Rossaint J, Block H, Bardel B, et al. Skap2 is required for ?2 integrin-mediated neutrophil recruitment and functions. J Exp Med. 2017;214:851-874 pubmed publisher
    ..Thus, Skap2 is essential to activate the ?2 integrins, and loss of Skap2 function is sufficient to cause a LAD-like phenotype in mice. ..
  17. Rognoni E, Ruppert R, Fässler R. The kindlin family: functions, signaling properties and implications for human disease. J Cell Sci. 2016;129:17-27 pubmed publisher
    ..syndrome (KS)--in which mainly skin and intestine are affected, whereas mutations in the KINDLIN-3 (also known as FERMT3) gene cause leukocyte adhesion deficiency type III (LAD III), which is characterized by impaired extravasation of ..
  18. Kikuchi T, Shibata Y, Kim H, Kubota Y, Yoshina S, Mitani S, et al. The BED finger domain protein MIG-39 halts migration of distal tip cells in Caenorhabditis elegans. Dev Biol. 2015;397:151-61 pubmed publisher
    ..We propose a model in which the anterior and posterior DTCs respond in an opposite manner to the levels of Rac activities in the cessation of DTC migration. ..
  19. Azorin P, Bonin F, Moukachar A, Ponceau A, Vacher S, Bieche I, et al. Distinct expression profiles and functions of Kindlins in breast cancer. J Exp Clin Cancer Res. 2018;37:281 pubmed publisher
    ..Kindlins may be useful in identifying breast cancer patients with a worst prognosis and may offer new avenues for therapeutic intervention against cancer progression. ..
  20. Morrison V, James M, Grześ K, Cook P, Glass D, Savinko T, et al. Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype. Nat Commun. 2014;5:5359 pubmed publisher
    ..Thus, ligand-reinforced beta2-integrin tail interactions restrict cytokine receptor signalling, survival, maturation and migration in myeloid cells and thereby contribute to immune homeostasis in vivo. ..
  21. Yates L, Gilbert R. Efficient production and purification of recombinant murine kindlin-3 from insect cells for biophysical studies. J Vis Exp. 2014;: pubmed publisher
    ..The same approach could be taken in the study of the other mammalian kindlin isoforms. ..
  22. Liao Z, Kato H, Pandey M, Cantor J, Ablooglu A, Ginsberg M, et al. Interaction of kindlin-2 with integrin β3 promotes outside-in signaling responses by the αVβ3 vitronectin receptor. Blood. 2015;125:1995-2004 pubmed publisher
    ..Thus, the β3/kindlin-2 interaction promotes outside-in αVβ3 signaling selectively, with biological consequences in vivo. ..
  23. Savinko T, Morrison V, Uotila L, Wolff C, Alenius H, Fagerholm S. Functional Beta2-Integrins Restrict Skin Inflammation In Vivo. J Invest Dermatol. 2015;135:2249-2257 pubmed publisher
    ..Functional beta2-integrins also have a major role in restricting the immune response in the inflamed skin and lymph nodes in vivo, likely through effects on mast cell and dendritic cell numbers and activation. ..
  24. Delyon J, Khayati F, Djaafri I, Podgorniak M, Sadoux A, Setterblad N, et al. EMMPRIN regulates β1 integrin-mediated adhesion through Kindlin-3 in human melanoma cells. Exp Dermatol. 2015;24:443-8 pubmed publisher
    ..To conclude, these findings reveal a new role of EMMPRIN in tumor cell migration through ß1 integrin/kindlin-3-mediated adhesion pathway. ..
  25. Margraf A, Nussbaum C, Rohwedder I, Klapproth S, Kurz A, Florian A, et al. Maturation of Platelet Function During Murine Fetal Development In Vivo. Arterioscler Thromb Vasc Biol. 2017;37:1076-1086 pubmed publisher
  26. Vanegas G, Lancien F, Leprince J, Vaudry H, Le Mével J. Effects of peripherally administered urotensin II and arginine vasotocin on the QT interval of the electrocardiogram in trout. Comp Biochem Physiol C Toxicol Pharmacol. 2016;183-184:53-60 pubmed publisher
    ..The effects of UII were compared to those of two structurally UII-related peptides (URPs), URP1 and URP2, and to those of arginine vasotocin (AVT), homolog of the mammalian arginine vasopressin...
  27. Meller J, Rogozin I, Poliakov E, Meller N, Bedanov Pack M, Plow E, et al. Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness. Mol Biol Cell. 2015;26:786-96 pubmed publisher
    ..Comparison of kindlin 2 (K2)/kindlin 3 (K3) chimeras revealed that the F2 subdomain, in particular its C-terminal part, is crucial for the differential ..
  28. Quan F, Dubessy C, Galant S, Kenigfest N, Djenoune L, Leprince J, et al. Comparative distribution and in vitro activities of the urotensin II-related peptides URP1 and URP2 in zebrafish: evidence for their colocalization in spinal cerebrospinal fluid-contacting neurons. PLoS ONE. 2015;10:e0119290 pubmed publisher
    ..peptides (URPs), such that the UII family is now known to include four paralogue genes called UII, URP, URP1 and URP2. These genes probably arose through the two rounds of whole genome duplication that occurred during early ..
  29. Ye F, Petrich B, Anekal P, Lefort C, Kasirer Friede A, Shattil S, et al. The mechanism of kindlin-mediated activation of integrin ?IIb?3. Curr Biol. 2013;23:2288-2295 pubmed publisher
    ..Thus, in contrast to talins, kindlins have little primary effect on integrin ?IIb?3 affinity for monovalent ligands and increase multivalent ligand binding by promoting the clustering of talin-activated integrins. ..
  30. Elgheznawy A, Shi L, Hu J, Wittig I, Laban H, Pircher J, et al. Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes. Circ Res. 2015;117:157-65 pubmed publisher
    ..Thus, calpain inhibition may be one means of normalizing platelet miRNA processing as well as platelet function in diabetes mellitus. ..
  31. Xu Y, Taru H, Jin Y, Quinn C. SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) function interdependently to promote axon guidance by regulating the MIG-2 GTPase. PLoS Genet. 2015;11:e1005185 pubmed publisher
    ..Our observations reveal a molecular mechanism that can allow two guidance receptors to function interdependently to regulate a common downstream effector, providing a potential means for the integration of guidance signals. ..
  32. Klapproth S, Moretti F, Zeiler M, Ruppert R, Breithaupt U, Mueller S, et al. Minimal amounts of kindlin-3 suffice for basal platelet and leukocyte functions in mice. Blood. 2015;126:2592-600 pubmed publisher
  33. Levy Strumpf N, Krizus M, Zheng H, Brown L, Culotti J. The Wnt Frizzled Receptor MOM-5 Regulates the UNC-5 Netrin Receptor through Small GTPase-Dependent Signaling to Determine the Polarity of Migrating Cells. PLoS Genet. 2015;11:e1005446 pubmed publisher
  34. Berrou E, Adam F, Lebret M, Planche V, Fergelot P, Issertial O, et al. Gain-of-Function Mutation in Filamin A Potentiates Platelet Integrin ?IIb?3 Activation. Arterioscler Thromb Vasc Biol. 2017;37:1087-1097 pubmed publisher
  35. Zheng C, Diaz Cuadros M, Chalfie M. GEFs and Rac GTPases control directional specificity of neurite extension along the anterior-posterior axis. Proc Natl Acad Sci U S A. 2016;113:6973-8 pubmed publisher
    ..Our study suggests that directional specificity of neurite extension is conferred through the intracellular activation of distinct GEFs and Rac GTPases. ..
  36. Martínez Moreno M, Leiva M, Aguilera Montilla N, Sevilla Movilla S, Isern de Val S, Arellano Sánchez N, et al. In vivo adhesion of malignant B cells to bone marrow microvasculature is regulated by α4β1 cytoplasmic-binding proteins. Leukemia. 2016;30:861-72 pubmed publisher
  37. Xu Z, Cai J, Gao J, White G, Chen F, Ma Y. Interaction of kindlin-3 and β2-integrins differentially regulates neutrophil recruitment and NET release in mice. Blood. 2015;126:373-7 pubmed publisher
  38. Walck Shannon E, Reiner D, Hardin J. Polarized Rac-dependent protrusions drive epithelial intercalation in the embryonic epidermis of C. elegans. Development. 2015;142:3549-60 pubmed publisher
    ..CRML-1 genetically suppresses UNC-73 function and, indirectly, actin polymerization. This network identifies a novel, molecularly conserved cassette that regulates epithelial intercalation via basolateral protrusive activity. ..
  39. Kato H, Nakazawa Y, Kurokawa Y, Kashiwagi H, Morikawa Y, Morita D, et al. Human CalDAG-GEFI deficiency increases bleeding and delays ?IIb?3 activation. Blood. 2016;128:2729-2733 pubmed
    ..Our results demonstrate the critical role of CalDAG-GEFI in rapid ?IIb?3 activation of human platelets. ..
  40. Yamahashi Y, Cavnar P, Hind L, Berthier E, Bennin D, Beebe D, et al. Integrin associated proteins differentially regulate neutrophil polarity and directed migration in 2D and 3D. Biomed Microdevices. 2015;17:100 pubmed publisher
    ..In a 3D environment, Kindlin-3 deficient cells displayed efficient chemotaxis. These findings demonstrate that the role of integrin regulatory proteins in cell polarity and directed migration can be different in 2D and 3D. ..
  41. Kondo N, Ueda Y, Kita T, Ozawa M, Tomiyama T, Yasuda K, et al. NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization. Mol Cell Biol. 2017;37: pubmed publisher
    ..Our findings reveal crucial roles for Rap1 signaling via NDR1 for recruitment of kindlin-3 and IS organization. ..
  42. Feng G, Zhu Z, Li W, Lin Q, Chai Y, Dong M, et al. Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans. EMBO J. 2017;36:334-345 pubmed publisher
    ..Therefore, we propose that the Hippo-RhoG feedback regulation maintains cell polarity during directional cell motility. ..
  43. Zhan J, Zhang H. Kindlins: Roles in development and cancer progression. Int J Biochem Cell Biol. 2018;98:93-103 pubmed publisher
    ..We also briefly descript the role of Kindlins in other diseases. Finally, we update the recent understanding of how Kindlins are regulated and modified as well as the degradation mechanism of Kindlins, respectively. ..
  44. Meakin P, Morrison V, Sneddon C, Savinko T, Uotila L, Jalicy S, et al. Mice Lacking beta2-Integrin Function Remain Glucose Tolerant in Spite of Insulin Resistance, Neutrophil Infiltration and Inflammation. PLoS ONE. 2015;10:e0138872 pubmed publisher
    ..Thus, beta2-integrins modulate glucose homeostasis during high fat feeding predominantly through actions on skeletal muscle to affect metabolic phenotype in vivo. ..
  45. Chua G, Tan S, Bhattacharjya S. NMR Characterization and Membrane Interactions of the Loop Region of Kindlin-3 F1 Subdomain. PLoS ONE. 2016;11:e0153501 pubmed publisher
    ..These data therefore provide important insights into the interactions of kindlin FERM domain with membrane lipids that contribute toward the integrin activating property. ..
  46. Qu J, Ero R, Feng C, Ong L, Tan H, Lee H, et al. Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells. Sci Rep. 2015;5:18491 pubmed publisher
    ..Mechanistically, kindlin-3 is involved in integrin α5ß1-Akt-mTOR-p70S6K signaling; however, its regulation of c-Myc protein expression could be independent of this signaling axis. ..
  47. van de Vijver E, Maddalena A, Sanal Ã, Holland S, Uzel G, Madkaikar M, et al. Hematologically important mutations: leukocyte adhesion deficiency (first update). Blood Cells Mol Dis. 2012;48:53-61 pubmed publisher
    ..This last syndrome is caused by mutations in FERMT3, encoding the kindlin-3 protein in all blood cells that is involved in the regulation of β integrin ..
  48. Oksala N, Pärssinen J, Seppälä I, Klopp N, Illig T, Laaksonen R, et al. Kindlin 3 (FERMT3) is associated with unstable atherosclerotic plaques, anti-inflammatory type II macrophages and upregulation of beta-2 integrins in all major arterial beds. Atherosclerosis. 2015;242:145-54 pubmed publisher
    ..In arterial plaques, both robustly expressed transcript variants of FERMT3 (MA: 5.90- and 3.4-fold; LDA: 3.99-fold, p < 0.0001 for all) and ITGB2 (MA: 4.81- and 4.92-fold; LDA: 5...
  49. Zhang H, Alshareef A, Wu C, Li S, Jiao J, Cao H, et al. Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism. Oncotarget. 2015;6:28949-60 pubmed publisher
    ..01). These data highlight that suppression of the Kindlin-2-integrin β1-AKT regulatory axis is an alternative mechanism underlying the tumor suppressor function of miR-200b in ESCC. ..
  50. Djaafri I, Khayati F, Menashi S, Tost J, Podgorniak M, Sadoux A, et al. A novel tumor suppressor function of Kindlin-3 in solid cancer. Oncotarget. 2014;5:8970-85 pubmed
    ..These data uncover a novel and unexpected tumor suppressor role of Kindlin-3 which can influence integrins targeted therapies development. ..
  51. Kasirer Friede A, Kang J, Kahner B, Ye F, Ginsberg M, Shattil S. ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding. Blood. 2014;123:3156-65 pubmed publisher
    ..Thus, ADAP uniquely promotes activation of and irreversible fibrinogen binding to platelet αIIbβ3 through interactions with talin and kindlin-3. ..
  52. Borgen M, Wang D, Grill B. RPM-1 regulates axon termination by affecting growth cone collapse and microtubule stability. Development. 2017;144:4658-4672 pubmed publisher
    ..These findings provide insight into how growth cone collapse is regulated during axon termination in vivo, and suggest that RPM-1 signaling destabilizes microtubules to facilitate growth cone collapse and axon termination. ..
  53. Morrison V, Macpherson M, Savinko T, Lek H, Prescott A, Fagerholm S. The ?2 integrin-kindlin-3 interaction is essential for T-cell homing but dispensable for T-cell activation in vivo. Blood. 2013;122:1428-36 pubmed publisher
  54. Xue Z, Feng C, Liu W, Tan S. A role of kindlin-3 in integrin ?M?2 outside-in signaling and the Syk-Vav1-Rac1/Cdc42 signaling axis. PLoS ONE. 2013;8:e56911 pubmed publisher
    ..We also show that kindlin-3 is required for the integrin ?M?2-Syk-Vav1 signaling axis that regulates Rac1 and Cdc42 activities. These findings reinforce a role for kindlin-3 in integrin outside-in signaling. ..
  55. Jurk K, Schulz A, Kehrel B, Rapple D, Schulze H, Möbest D, et al. Novel integrin-dependent platelet malfunction in siblings with leukocyte adhesion deficiency-III (LAD-III) caused by a point mutation in FERMT3. Thromb Haemost. 2010;103:1053-64 pubmed publisher
    ..platelet dysfunction in two brothers with LAD-III syndrome caused by a homozygous mutation 1717C>T in the FERMT3 gene leading to a premature stop codon R573X in the focal adhesion protein kindlin-3...
  56. Willenbrock F, Zicha D, Hoppe A, Hogg N. Novel automated tracking analysis of particles subjected to shear flow: kindlin-3 role in B cells. Biophys J. 2013;105:1110-22 pubmed publisher
    ..Our evidence indicates that kindlin-3-mediated high-affinity LFA-1 controls both the early transient integrin-dependent adhesions in addition to the final stable adhesions made under flow conditions. ..
  57. Lu L, Lin C, Yan Z, Wang S, Zhang Y, Wang S, et al. Kindlin-3 Is Essential for the Resting ?4?1 Integrin-mediated Firm Cell Adhesion under Shear Flow Conditions. J Biol Chem. 2016;291:10363-71 pubmed publisher
    ..Defective kindlin-3 binding to the resting ?4?1 leads to a transition from firm to rolling cell adhesion on VCAM-1, implying its potential role in regulating the transition between integrin-mediated rolling and firm cell adhesion. ..
  58. Ruppert R, Moser M, Sperandio M, Rognoni E, Orban M, Liu W, et al. Kindlin-3-mediated integrin adhesion is dispensable for quiescent but essential for activated hematopoietic stem cells. J Exp Med. 2015;212:1415-32 pubmed publisher
    ..The accumulation of HSPCs in the circulation of leukocyte adhesion deficiency type III patients, who lack Kindlin-3, underlines the conserved functions of Kindlin-3 in man and the importance of our findings for human disease. ..
  59. Lu C, Cui C, Liu B, Zou S, Song H, Tian H, et al. FERMT3 contributes to glioblastoma cell proliferation and chemoresistance to temozolomide through integrin mediated Wnt signaling. Neurosci Lett. 2017;657:77-83 pubmed publisher
    b>FERMT3, also known as kindlin-3, is one of three kindlin family members expressed in mammals. Kindlins are cytosolic, adaptor proteins that are important activators and regulators of integrin function...
  60. Gao J, Huang M, Lai J, Mao K, Sun P, Cao Z, et al. Kindlin supports platelet integrin αIIbβ3 activation by interacting with paxillin. J Cell Sci. 2017;130:3764-3775 pubmed publisher
    ..Taken together, our findings uncover a novel mechanism by which kindlin supports integrin αIIbβ3 activation, which might be beneficial for developing safer anti-thrombotic therapies. ..
  61. Boyd R, Adam P, Patel S, Loader J, Berry J, Redpath N, et al. Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B. Leukemia. 2003;17:1605-12 pubmed
    ..We also describe two novel proteins (MIG2B and B-cell novel protein #1, BCNP1), which are expressed preferentially in B cells...
  62. Nakazawa T, Tadokoro S, Kamae T, Kiyomizu K, Kashiwagi H, Honda S, et al. Agonist stimulation, talin-1, and kindlin-3 are crucial for ?(IIb)?(3) activation in a human megakaryoblastic cell line, CMK. Exp Hematol. 2013;41:79-90.e1 pubmed publisher
    ..We proposed that the CMK cell line is an attractive platform for investigating agonist-, talin-1-, and kindlin-3- dependent ?(IIb)?(3) activation. ..
  63. He Y, Sonnenwald T, Sprenger A, Hansen U, Dengjel J, Bruckner Tuderman L, et al. RhoA activation by CNFy restores cell-cell adhesion in kindlin-2-deficient keratinocytes. J Pathol. 2014;233:269-80 pubmed publisher
    ..Our results suggest that pharmacological regulation of RhoGTPase activity may represent a therapeutic option for skin fragility. ..
  64. Gruda R, Brown A, Grabovsky V, Mizrahi S, Gur C, Feigelson S, et al. Loss of kindlin-3 alters the threshold for NK cell activation in human leukocyte adhesion deficiency-III. Blood. 2012;120:3915-24 pubmed publisher
    ..The realization that NK cell activity is impaired, but not absent in leukocyte adhesion deficiency, may lead to the development of more efficient therapy for this rare disease. ..
  65. Meller J, Malinin N, Panigrahi S, Kerr B, Patil A, Ma Y, et al. Novel aspects of Kindlin-3 function in humans based on a new case of leukocyte adhesion deficiency III. J Thromb Haemost. 2012;10:1397-408 pubmed publisher
    ..Abnormalities in glycoprotein Ib-IX function in Kindlin-3-deficient platelets are secondary to integrin defects. The region of Kindlin-3 encoded by exon 11 is crucial for its ability to activate integrins in humans. ..
  66. Fröbel J, Cadeddu R, Hartwig S, Bruns I, Wilk C, Kundgen A, et al. Platelet proteome analysis reveals integrin-dependent aggregation defects in patients with myelodysplastic syndromes. Mol Cell Proteomics. 2013;12:1272-80 pubmed publisher
  67. Bialkowska K, Byzova T, Plow E. Site-specific phosphorylation of kindlin-3 protein regulates its capacity to control cellular responses mediated by integrin αIIbβ3. J Biol Chem. 2015;290:6226-42 pubmed publisher
    ..These data identify a role of kindlin-3 phosphorylation in integrin β3 activation and provide a basis for functional differences between kindlin-3 and the two other kindlin paralogs. ..
  68. Harris E, Smith T, Springett G, Weyrich A, Zimmerman G. Leukocyte adhesion deficiency-I variant syndrome (LAD-Iv, LAD-III): molecular characterization of the defect in an index family. Am J Hematol. 2012;87:311-3 pubmed publisher
    ..Here, we show that the molecular defect in this index subject is a new mutation in FERMT3 (KINDLIN-3) which encodes KINDLIN-3, a cytoskeletal protein that interacts with the cytoplasmic tails of ??, ??, ..
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    ..Taken together, our findings demonstrated that TGF-β1-induced Kindlin-2 expression promotes PDAC progression by downregulation of HOXB9 and E-cadherin. ..
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    ..Fermitin Family Member 3 (FERMT3) gene, which was predicted to disrupt the functionality of its protein product kindlin 3. Our report provides information relevant to physicians for recognizing patients with one of the rarest forms of ..
  72. Shiratori T, Kyumoto Nakamura Y, Kukita A, Uehara N, Zhang J, Koda K, et al. IL-1? Induces Pathologically Activated Osteoclasts Bearing Extremely High Levels of Resorbing Activity: A Possible Pathological Subpopulation of Osteoclasts, Accompanied by Suppressed Expression of Kindlin-3 and Talin-1. J Immunol. 2018;200:218-228 pubmed publisher
    ..PAOCs could form a subpopulation of osteoclasts possibly different from normal osteoclasts. PAOC-specific molecules could be an ideal target for regulating pathological bone destruction. ..
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    ..From these studies we conclude that FMO-1, FMO-4, FMO-5, and EHBP-1 represent new players downstream of UNC-6/Netrin receptors and Rac GTPases that inhibit growth cone filopodial protrusion in repulsive axon guidance. ..
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    ..Just recently mutations in Kindlin 3, a newly recognized component, which binds the cytoplasmic tail of integrin, and is important in integrin ..
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    ..of the Ca2+ channel ORAI1, stromal interaction molecule 1 (STIM1) or integrin-regulating kindlin-3 (FERMT3), severe immunodeficiency is frequently linked to abnormal platelet activity...
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    ..Kindlin‑2 may regulate CCRCC progression through the Wnt signaling pathway, promoting CCRCC cell proliferation, migration and invasion. ..
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    ..Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients. ..
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    The protein kindlin 3 is mutated in the leukocyte adhesion deficiency III (LAD-III) disorder, leading to widespread infection due to the failure of leukocytes to migrate into infected tissue sites...
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    ..This represents a novel mechanism regulating reversibility of integrin adhesion complexes in leukocytes, which, in turn, is critical for their successful transmigration through the extracellular matrix. ..
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    ..We found suggestive evidence for developmentally expressed genes operant in hippocampal dependent memory and learning with the CBCL-DP. ..
  83. Ou Y, Zhao Z, Wu C, Xu B, Song Y, Zhan Q. Mig-2 attenuates cisplatin-induced apoptosis of human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways. Acta Pharmacol Sin. 2014;35:1199-206 pubmed publisher
    ..Mig-2 significantly attenuates the antitumor action of cisplatin against human glioma cells in vitro through AKT/JNK and AKT/p38 signaling pathways. The F3 subdomain of mig-2 is necessary and sufficient for this effect. ..
  84. Crazzolara R, Maurer K, Schulze H, Zieger B, Zustin J, Schulz A. A new mutation in the KINDLIN-3 gene ablates integrin-dependent leukocyte, platelet, and osteoclast function in a patient with leukocyte adhesion deficiency-III. Pediatr Blood Cancer. 2015;62:1677-9 pubmed publisher
    ..In this study, we identified a new C>T point mutation in exon 13 in the FERMT3 gene in an infant diagnosed with LAD-III and showed that KINDLIN-3 expression is required for platelet aggregation ..
  85. Hyduk S, Rullo J, Cano A, Xiao H, Chen M, Moser M, et al. Talin-1 and kindlin-3 regulate alpha4beta1 integrin-mediated adhesion stabilization, but not G protein-coupled receptor-induced affinity upregulation. J Immunol. 2011;187:4360-8 pubmed publisher
    ..Talin-1 contributed to ?(4)?(1)-dependent chemotaxis, suggesting that it participates in a later stage of the leukocyte adhesion cascade when the leukocyte cytoskeleton undergoes dramatic rearrangement...
  86. Sossey Alaoui K, Pluskota E, Davuluri G, Bialkowska K, Das M, Szpak D, et al. Kindlin-3 enhances breast cancer progression and metastasis by activating Twist-mediated angiogenesis. FASEB J. 2014;28:2260-71 pubmed publisher
    ..This signaling cascade enhances breast cancer cell invasion and tumor angiogenesis and metastasis. ..
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    ..Analyzing human bone biopsies of rare skeletal disorders might improve our understanding of bone metabolism with possible implications for the clinical management of other bone diseases. ..
  88. Suratannon N, Yeetong P, Srichomthong C, Amarinthnukrowh P, Chatchatee P, Sosothikul D, et al. Adaptive immune defects in a patient with leukocyte adhesion deficiency type III with a novel mutation in FERMT3. Pediatr Allergy Immunol. 2016;27:214-7 pubmed publisher
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  90. Feigelson S, Grabovsky V, Manevich Mendelson E, Pasvolsky R, Shulman Z, Shinder V, et al. Kindlin-3 is required for the stabilization of TCR-stimulated LFA-1:ICAM-1 bonds critical for lymphocyte arrest and spreading on dendritic cells. Blood. 2011;117:7042-52 pubmed publisher
    ..We suggest that Kindlin-3 selectively contributes to a final TCR-triggered outside-in stabilization of bonds generated between chemokine-primed LFA-1 molecules and cell-surface ICAM-1. ..
  91. Yang M, Du J, Lu D, Ren C, Shen H, Qiao J, et al. Increased expression of kindlin 2 in luteinized granulosa cells correlates with androgen receptor level in patients with polycystic ovary syndrome having hyperandrogenemia. Reprod Sci. 2014;21:696-703 pubmed publisher
    ..Taken together, kindlin 2 may play a role in luteinized GCs, especially in the case of excess androgen. Further studies are required to assess the specific role of kindlin 2 in follicular development and PCOS pathogenesis. ..