2o26 › Citations

Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.

Liu H, Chen X, Focia PJ, He X
EMBO J 26 891-901 (2007)
Cited: 63 times
EuropePMC logo PMID: 17255936

Abstract

Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of KIT activation is associated with many cancers. We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilitate each of its first three immunoglobulin (Ig)-like domains to interact with SCF. Three surface epitopes on SCF, an extended loop, the B and C helices, and the N-terminal segment, contact distinct KIT domains, with two of the epitopes undergoing large conformational changes upon receptor binding. The SCF/KIT complex reveals a unique RTK dimerization assembly, and a novel recognition mode between four-helix bundle cytokines and Ig-family receptors. It serves as a framework for understanding the activation mechanisms of class III RTKs.

Articles - 2o26 mentioned but not cited (4)

  1. Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases. Liu H, Chen X, Focia PJ, He X. EMBO J 26 891-901 (2007)
  2. Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling. Ho CCM, Chhabra A, Starkl P, Schnorr PJ, Wilmes S, Moraga I, Kwon HS, Gaudenzio N, Sibilano R, Wehrman TS, Gakovic M, Sockolosky JT, Tiffany MR, Ring AM, Piehler J, Weissman IL, Galli SJ, Shizuru JA, Garcia KC. Cell 168 1041-1052.e18 (2017)
  3. Spatial distribution and receptor specificity of zebrafish Kit system--evidence for a Kit-mediated bi-directional communication system in the preovulatory ovarian follicle. Yao K, Ge W. PLoS One 8 e56192 (2013)
  4. Cross-strand disulfides in the hydrogen bonding site of antiparallel β-sheet (aCSDhs): Forbidden disulfides that are highly strained, easily broken. Haworth NL, Wouters MJ, Hunter MO, Ma L, Wouters MA. Protein Sci 28 239-256 (2019)


Reviews citing this publication (14)

  1. Cell signaling by receptor tyrosine kinases. Lemmon MA, Schlessinger J. Cell 141 1117-1134 (2010)
  2. Molecular pathobiology of gastrointestinal stromal sarcomas. Corless CL, Heinrich MC. Annu Rev Pathol 3 557-586 (2008)
  3. Structure-based view of epidermal growth factor receptor regulation. Ferguson KM. Annu Rev Biophys 37 353-373 (2008)
  4. Platelet-derived growth factors and their receptors: structural and functional perspectives. Chen PH, Chen X, He X. Biochim Biophys Acta 1834 2176-2186 (2013)
  5. Structural biology of glycoprotein hormones and their receptors: insights to signaling. Jiang X, Dias JA, He X. Mol Cell Endocrinol 382 424-451 (2014)
  6. Extracellular assembly and activation principles of oncogenic class III receptor tyrosine kinases. Verstraete K, Savvides SN. Nat Rev Cancer 12 753-766 (2012)
  7. Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors. Pittoni P, Piconese S, Tripodo C, Colombo MP. Oncogene 30 757-769 (2011)
  8. Structural studies of GDNF family ligands with their receptors-Insights into ligand recognition and activation of receptor tyrosine kinase RET. Wang X. Biochim Biophys Acta 1834 2205-2212 (2013)
  9. The SCF/c-KIT system in the male: Survival strategies in fertility and cancer. Cardoso HJ, Figueira MI, Correia S, Vaz CV, Socorro S. Mol Reprod Dev 81 1064-1079 (2014)
  10. Class III Receptor Tyrosine Kinases in Acute Leukemia - Biological Functions and Modern Laboratory Analysis. Berenstein R. Biomark Insights 10 1-14 (2015)
  11. Activated leukemic oncogenes AML1-ETO and c-kit: role in development of acute myeloid leukemia and current approaches for their inhibition. Rulina AV, Spirin PV, Prassolov VS. Biochemistry (Mosc) 75 1650-1666 (2010)
  12. Tropomyosin-receptor-kinases signaling in the nervous system. Stoleru B, Popescu AM, Tache DE, Neamtu OM, Emami G, Tataranu LG, Buteica AS, Dricu A, Purcaru SO. Maedica (Bucur) 8 43-48 (2013)
  13. Principal signalling complexes in haematopoiesis: structural aspects and mimetic discovery. Tarasova A, Haylock D, Winkler D. Cytokine Growth Factor Rev 22 231-253 (2011)
  14. Structural Perspectives on Extracellular Recognition and Conformational Changes of Several Type-I Transmembrane Receptors. Chataigner LMP, Leloup N, Janssen BJC. Front Mol Biosci 7 129 (2020)

Articles citing this publication (45)

  1. Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex. Shim AH, Liu H, Focia PJ, Chen X, Lin PC, He X. Proc Natl Acad Sci U S A 107 11307-11312 (2010)
  2. Structural basis for the dual recognition of helical cytokines IL-34 and CSF-1 by CSF-1R. Ma X, Lin WY, Chen Y, Stawicki S, Mukhyala K, Wu Y, Martin F, Bazan JF, Starovasnik MA. Structure 20 676-687 (2012)
  3. The mechanism of shared but distinct CSF-1R signaling by the non-homologous cytokines IL-34 and CSF-1. Liu H, Leo C, Chen X, Wong BR, Williams LT, Lin H, He X. Biochim Biophys Acta 1824 938-945 (2012)
  4. Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex. Verstraete K, Vandriessche G, Januar M, Elegheert J, Shkumatov AV, Desfosses A, Van Craenenbroeck K, Svergun DI, Gutsche I, Vergauwen B, Savvides SN. Blood 118 60-68 (2011)
  5. Mutation D816V alters the internal structure and dynamics of c-KIT receptor cytoplasmic region: implications for dimerization and activation mechanisms. Laine E, Chauvot de Beauchêne I, Perahia D, Auclair C, Tchertanov L. PLoS Comput Biol 7 e1002068 (2011)
  6. Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells. Chaix A, Lopez S, Voisset E, Gros L, Dubreuil P, De Sepulveda P. J Biol Chem 286 5956-5966 (2011)
  7. Structure of macrophage colony stimulating factor bound to FMS: diverse signaling assemblies of class III receptor tyrosine kinases. Chen X, Liu H, Focia PJ, Shim AH, He X. Proc Natl Acad Sci U S A 105 18267-18272 (2008)
  8. Transmembrane domain-mediated orientation of receptor monomers in active VEGFR-2 dimers. Dosch DD, Ballmer-Hofer K. FASEB J 24 32-38 (2010)
  9. Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are driven by common assembly principles. Elegheert J, Desfosses A, Shkumatov AV, Wu X, Bracke N, Verstraete K, Van Craenenbroeck K, Brooks BR, Svergun DI, Vergauwen B, Gutsche I, Savvides SN. Structure 19 1762-1772 (2011)
  10. Structure of Full-Length Human PDGFRβ Bound to Its Activating Ligand PDGF-B as Determined by Negative-Stain Electron Microscopy. Chen PH, Unger V, He X. J Mol Biol 427 3921-3934 (2015)
  11. Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers. Opatowsky Y, Lax I, Tomé F, Bleichert F, Unger VM, Schlessinger J. Proc Natl Acad Sci U S A 111 1772-1777 (2014)
  12. Structural and functional characterization of alternative transmembrane domain conformations in VEGF receptor 2 activation. Manni S, Mineev KS, Usmanova D, Lyukmanova EN, Shulepko MA, Kirpichnikov MP, Winter J, Matkovic M, Deupi X, Arseniev AS, Ballmer-Hofer K. Structure 22 1077-1089 (2014)
  13. Strong oligomerization behavior of PDGFbeta receptor transmembrane domain and its regulation by the juxtamembrane regions. Oates J, King G, Dixon AM. Biochim Biophys Acta 1798 605-615 (2010)
  14. The strength and cooperativity of KIT ectodomain contacts determine normal ligand-dependent stimulation or oncogenic activation in cancer. Reshetnyak AV, Opatowsky Y, Boggon TJ, Folta-Stogniew E, Tome F, Lax I, Schlessinger J. Mol Cell 57 191-201 (2015)
  15. Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1. Shim AH, Chang RA, Chen X, Longnecker R, He X. Proc Natl Acad Sci U S A 109 12962-12967 (2012)
  16. Structural basis for KIT receptor tyrosine kinase inhibition by antibodies targeting the D4 membrane-proximal region. Reshetnyak AV, Nelson B, Shi X, Boggon TJ, Pavlenco A, Mandel-Bausch EM, Tome F, Suzuki Y, Sidhu SS, Lax I, Schlessinger J. Proc Natl Acad Sci U S A 110 17832-17837 (2013)
  17. Dimerization of Kit-ligand and efficient cell-surface presentation requires a conserved Ser-Gly-Gly-Tyr motif in its transmembrane domain. Paulhe F, Wehrle-Haller M, Jacquier MC, Imhof BA, Tabone-Eglinger S, Wehrle-Haller B. FASEB J 23 3037-3048 (2009)
  18. Mechanism of activation of human c-KIT kinase by internal tandem duplications of the juxtamembrane domain and point mutations at aspartic acid 816. Kim SY, Kang JJ, Lee HH, Kang JJ, Kim B, Kim CG, Park TK, Kang H. Biochem Biophys Res Commun 410 224-228 (2011)
  19. Study of c-kit immunoexpression in canine cutaneous melanocytic tumors. Gomes J, Queiroga FL, Prada J, Pires I. Melanoma Res 22 195-201 (2012)
  20. A new twist in the transmembrane signaling tool-kit. Lemmon MA, Ferguson KM. Cell 130 213-215 (2007)
  21. Residues 39-56 of Stem Cell Factor Protein Sequence Are Capable of Stimulating the Expansion of Cord Blood CD34+ Cells. Shen B, Jiang W, Fan J, Dai W, Ding X, Jiang Y. PLoS One 10 e0141485 (2015)
  22. Stem cell factor and NSC87877 combine to enhance c-Kit mediated proliferation of human megakaryoblastic cells. Raghav PK, Singh AK, Gangenahalli G. PLoS One 13 e0206364 (2018)
  23. Screening for key lncRNAs in the progression of gallbladder cancer using bioinformatics analyses. Zhang L, Geng Z, Meng X, Meng F, Wang L. Mol Med Rep 17 6449-6455 (2018)
  24. Interstitial Cells of Cajal: Pathology, injury and repair. Al-Sajee D, Huizinga JD. Sultan Qaboos Univ Med J 12 411-421 (2012)
  25. Engineered variants of InlB with an additional leucine-rich repeat discriminate between physiologically relevant and packing contacts in crystal structures of the InlB:MET complex. Niemann HH, Gherardi E, Bleymüller WM, Heinz DW. Protein Sci 21 1528-1539 (2012)
  26. Genetic variation at KIT locus may predispose to melanoma. Bourillon A, Hu HH, Hetet G, Lacapere JJ, André J, Descamps V, Basset-Seguin N, Ogbah Z, Puig S, Saiag P, Bagot M, Bensussan A, Grandchamp B, Dumaz N, Soufir N. Pigment Cell Melanoma Res 26 88-96 (2013)
  27. KIT and melanoma predisposition in pigs: sequence variants and association analysis. Fernández-Rodríguez A, Estellé J, Blin A, Muñoz M, Créchet F, Demenais F, Vincent-Naulleau S, Bourneuf E. Anim Genet 45 445-448 (2014)
  28. Molecular analysis of WT1 and KIT mutations in patients from an Indian population with de novo acute myeloid leukemia: determination of incidence, distribution patterns, and report of a novel KIT mutation. Ahmad F, D'Souza W, Mandava S, Das BR. Leuk Lymphoma 52 865-876 (2011)
  29. Where are the theca cells from: the mechanism of theca cells derivation and differentiation. Liu T, Qin QY, Qu JX, Wang HY, Yan J. Chin Med J (Engl) 133 1711-1718 (2020)
  30. Cancer cell motility is affected through 3D cell culturing and SCF/c-Kit pathway but not by X-irradiation. Eberle F, Saulich MF, Leinberger FH, Seeger W, Engenhart-Cabillic R, Dikomey E, Hänze J, Hattar K, Subtil FS. Radiother Oncol 119 537-543 (2016)
  31. Hypoxia and MITF regulate KIT oncogenic properties in melanocytes. Laugier F, Delyon J, André J, Bensussan A, Dumaz N. Oncogene 35 5070-5077 (2016)
  32. Full-length recombinant human SCF1-165 is more thermostable than the truncated SCF1-141 form. Weng YP, Ku WY, Wu MH, Tsai YL, Chen CY, Kuo CA, Huang LL. PLoS One 9 e103251 (2014)
  33. In cancer cell lines inhibition of SCF/c-Kit pathway leads to radiosensitization only when SCF is strongly over-expressed. Eberle F, Leinberger FH, Saulich MF, Seeger W, Engenhart-Cabillic R, Hänze J, Hattar K, Dikomey E, Subtil FSB. Clin Transl Radiat Oncol 2 69-75 (2017)
  34. Microarray profiling of gene expression in human keratinocytes suggests a new protective activity against UV-induced DNA damage for a compound previously known to interact with SCF-KIT signalling pathway. Serre C, Lebleu A, Bergeron L, Plantivaux A, Botto JM, Dal Farra C, Domloge N. Int J Cosmet Sci 33 398-407 (2011)
  35. Stem cell factor is implicated in microenvironmental interactions and cellular dynamics of chronic lymphocytic leukemia. Gavriilidis GI, Ntoufa S, Papakonstantinou N, Kotta K, Koletsa T, Chartomatsidou E, Moysiadis T, Stavroyianni N, Anagnostopoulos A, Papadaki E, Tsiftsoglou AS, Stamatopoulos K. Haematologica 106 692-700 (2021)
  36. Cell population modelling describes intrinsic heterogeneity: a case study for hematopoietic stem cells. Luni C, Doyle FJ, Elvassore N. IET Syst Biol 5 164-173 (2011)
  37. Comparison of lesional skin c-KIT mutations with clinical phenotype in patients with mastocytosis. Chan IJ, Tharp MD. Clin Exp Dermatol 43 416-422 (2018)
  38. Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention. Krimmer SG, Bertoletti N, Suzuki Y, Katic L, Mohanty J, Shu S, Lee S, Lax I, Mi W, Schlessinger J. Proc Natl Acad Sci U S A 120 e2300054120 (2023)
  39. Mutation in the first Ig-like domain of Kit leads to JAK2 activation and myeloproliferation in mice. Huang Z, Ruan HB, Zhang ZD, Chen W, Lin Z, Zeng H, Gao X. Am J Pathol 184 122-132 (2014)
  40. A fully human anti-c-Kit monoclonal antibody 2G4 inhibits proliferation and degranulation of human mast cells. Kim KH, Kim JO, Park SG. Mol Cell Biochem 478 861-873 (2023)
  41. Cloning of Soluble Human Stem Cell Factor in pET-26b(+) Vector. Asghari S, Shekari Khaniani M, Darabi M, Mansoori Derakhshan S. Adv Pharm Bull 4 91-95 (2014)
  42. The blood proteome of imminent lung cancer diagnosis. Lung Cancer Cohort Consortium (LC3). Nat Commun 14 3042 (2023)
  43. An effective strategy for ligand-mediated pulldown of the HER2/HER3/NRG1β heterocomplex and cryo-EM structure determination at low sample concentrations. Trenker R, Diwanji D, Verba KA, Jura N. Methods Enzymol 667 633-662 (2022)
  44. DAZAP1 facilitates the alternative splicing of KITLG to promote multiple myeloma cell proliferation via ERK signaling pathway. Zhou Y, Huangfu S, Li M, Tang C, Qian J, Guo M, Zhou Z, Yang Y, Gu C. Aging (Albany NY) 14 7972-7985 (2022)
  45. Multiple intratumoral sources of kit ligand promote gastrointestinal stromal tumor. Tieniber AD, Rossi F, Hanna AN, Liu M, Etherington MS, Loo JK, Param N, Zeng S, Do K, Wang L, DeMatteo RP. Oncogene 42 2578-2588 (2023)


Quick links