1b47 › Citations

Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase.

Meng W, Sawasdikosol S, Burakoff SJ, Eck MJ
Nature 398 84-90 (1999)
Cited: 177 times
EuropePMC logo PMID: 10078535

Abstract

Cbl is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface. The evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to phosphorylated tyrosine residues and has cell-transforming activity. Point mutations in Cbl that disrupt its recognition of phosphotyrosine also interfere with its negative regulatory function and, in the case of v-cbl, with its oncogenic potential. In T cells, Cbl-N binds to the tyrosine-phosphorylated inhibitory site of the protein tyrosine kinase ZAP-70. Here we describe the crystal structure of Cbl-N, both alone and in complex with a phosphopeptide that represents its binding site in ZAP-70. The structures show that Cbl-N is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium-binding domain, and a divergent SH2 domain that was not recognizable from the amino-acid sequence of the protein. The calcium-bound EF hand wedges between the 4H and SH2 domains and roughly determines their relative orientation. In the ligand-occupied structure, the 4H domain packs against the SH2 domain and completes its phosphotyrosine-recognition pocket. Disruption of this binding to ZAP-70 as a result of structure-based mutations in the 4H, EF-hand and SH2 domains confirms that the three domains together form an integrated phosphoprotein-recognition module.

Articles - 1b47 mentioned but not cited (5)

  1. Massive peptide sharing between viral and human proteomes. Kanduc D, Stufano A, Lucchese G, Kusalik A. Peptides 29 1755-1766 (2008)
  2. A mass weighted chemical elastic network model elucidates closed form domain motions in proteins. Kim MH, Seo S, Jeong JI, Kim BJ, Liu WK, Lim BS, Choi JB, Kim MK. Protein Sci 22 605-613 (2013)
  3. Protein flexibility: coordinate uncertainties and interpretation of structural differences. Rashin AA, Rashin AH, Jernigan RL. Acta Crystallogr D Biol Crystallogr 65 1140-1161 (2009)
  4. Phosphorylation control of the ubiquitin ligase Cbl is conserved in choanoflagellates. Amacher JF, Hobbs HT, Cantor AC, Shah L, Rivero MJ, Mulchand SA, Kuriyan J. Protein Sci 27 923-932 (2018)
  5. Sleuthing biochemical evidence to elucidate unassigned electron density in a CBL-SLAP2 crystal complex. Wybenga-Groot LE, McGlade CJ. Acta Crystallogr F Struct Biol Commun 77 37-46 (2021)


Reviews citing this publication (48)

  1. Signaling--2000 and beyond. Hunter T. Cell 100 113-127 (2000)
  2. Ubiquitin Ligases: Structure, Function, and Regulation. Zheng N, Shabek N. Annu Rev Biochem 86 129-157 (2017)
  3. Cbl: many adaptations to regulate protein tyrosine kinases. Thien CB, Langdon WY. Nat Rev Mol Cell Biol 2 294-307 (2001)
  4. Regulatory and signaling properties of the Vav family. Bustelo XR. Mol Cell Biol 20 1461-1477 (2000)
  5. RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Metzger MB, Pruneda JN, Klevit RE, Weissman AM. Biochim Biophys Acta 1843 47-60 (2014)
  6. Signal transduction by the TCR for antigen. Kane LP, Lin J, Weiss A. Curr Opin Immunol 12 242-249 (2000)
  7. The tyrosine kinase network regulating mast cell activation. Gilfillan AM, Rivera J. Immunol Rev 228 149-169 (2009)
  8. Phosphotyrosine-binding domains in signal transduction. Yaffe MB. Nat Rev Mol Cell Biol 3 177-186 (2002)
  9. Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases. Waterman H, Yarden Y. FEBS Lett 490 142-152 (2001)
  10. The Cbl family proteins: ring leaders in regulation of cell signaling. Swaminathan G, Tsygankov AY. J Cell Physiol 209 21-43 (2006)
  11. c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses. Thien CB, Langdon WY. Biochem J 391 153-166 (2005)
  12. Diversity of conformational states and changes within the EF-hand protein superfamily. Yap KL, Ames JB, Swindells MB, Ikura M. Proteins 37 499-507 (1999)
  13. SH2 and PTB domains in tyrosine kinase signaling. Schlessinger J, Lemmon MA. Sci STKE 2003 RE12 (2003)
  14. Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases. Mohapatra B, Ahmad G, Nadeau S, Zutshi N, An W, Scheffe S, Dong L, Feng D, Goetz B, Arya P, Bailey TA, Palermo N, Borgstahl GE, Natarajan A, Raja SM, Naramura M, Band V, Band H. Biochim Biophys Acta 1833 122-139 (2013)
  15. Tyrosine kinase inhibitors targeted to the epidermal growth factor receptor subfamily: role as anticancer agents. Noonberg SB, Benz CC. Drugs 59 753-767 (2000)
  16. Positive and negative regulation of T-cell activation by adaptor proteins. Koretzky GA, Myung PS. Nat Rev Immunol 1 95-107 (2001)
  17. The Cbl family and other ubiquitin ligases: destructive forces in control of antigen receptor signaling. Duan L, Reddi AL, Ghosh A, Dimri M, Band H. Immunity 21 7-17 (2004)
  18. The Cbl protooncoprotein: a negative regulator of immune receptor signal transduction. Lupher ML, Rao N, Eck MJ, Band H. Immunol Today 20 375-382 (1999)
  19. Beyond the RING: CBL proteins as multivalent adapters. Tsygankov AY, Teckchandani AM, Feshchenko EA, Swaminathan G. Oncogene 20 6382-6402 (2001)
  20. Interaction domains: from simple binding events to complex cellular behavior. Pawson T, Raina M, Nash P. FEBS Lett 513 2-10 (2002)
  21. Lymphocytes with a complex: adapter proteins in antigen receptor signaling. Tomlinson MG, Lin J, Weiss A. Immunol Today 21 584-591 (2000)
  22. Diversity in protein recognition by PTB domains. Forman-Kay JD, Pawson T. Curr Opin Struct Biol 9 690-695 (1999)
  23. The language of SH2 domain interactions defines phosphotyrosine-mediated signal transduction. Liu BA, Engelmann BW, Nash PD. FEBS Lett 586 2597-2605 (2012)
  24. Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor tyrosine kinase signaling. Wagner MJ, Stacey MM, Liu BA, Pawson T. Cold Spring Harb Perspect Biol 5 a008987 (2013)
  25. ZAP-70 in Signaling, Biology, and Disease. Au-Yeung BB, Shah NH, Shen L, Weiss A. Annu Rev Immunol 36 127-156 (2018)
  26. Finding function through structural genomics. Shapiro L, Harris T. Curr Opin Biotechnol 11 31-35 (2000)
  27. Ars Moriendi; the art of dying well - new insights into the molecular pathways of necroptotic cell death. Murphy JM, Silke J. EMBO Rep 15 155-164 (2014)
  28. Modulation of Immune Cell Functions by the E3 Ligase Cbl-b. Lutz-Nicoladoni C, Wolf D, Sopper S. Front Oncol 5 58 (2015)
  29. Macromolecular juggling by ubiquitylation enzymes. Lorenz S, Cantor AJ, Rape M, Kuriyan J. BMC Biol 11 65 (2013)
  30. Molecular controls of antigen receptor clustering and autoimmunity. Krawczyk C, Penninger JM. Trends Cell Biol 11 212-220 (2001)
  31. Regulation of immune responses by E3 ubiquitin ligase Cbl-b. Tang R, Langdon WY, Zhang J. Cell Immunol 340 103878 (2019)
  32. E3 ubiquitin ligase Cbl-b in innate and adaptive immunity. Liu Q, Zhou H, Langdon WY, Zhang J. Cell Cycle 13 1875-1884 (2014)
  33. The Cbl family: ubiquitin ligases regulating signaling by tyrosine kinases. Sanjay A, Horne WC, Baron R. Sci STKE 2001 pe40 (2001)
  34. Spleen tyrosine kinase: an Src family of non-receptor kinase has multiple functions and represents a valuable therapeutic target in the treatment of autoimmune and inflammatory diseases. Ghosh D, Tsokos GC. Autoimmunity 43 48-55 (2010)
  35. Cell regulation by phosphotyrosine-targeted ubiquitin ligases. Cooper JA, Kaneko T, Li SS. Mol Cell Biol 35 1886-1897 (2015)
  36. Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b. Loeser S, Penninger JM. Semin Immunol 19 206-214 (2007)
  37. Manifestations of multicellularity: Dictyostelium reports in. Williams JG, Noegel AA, Eichinger L. Trends Genet 21 392-398 (2005)
  38. Intracellular adapter molecules. Norian LA, Koretzky GA. Semin Immunol 12 43-54 (2000)
  39. Structural and functional diversity of adaptor proteins involved in tyrosine kinase signalling. Csiszár A. Bioessays 28 465-479 (2006)
  40. Adapting to multiple personalities: Cbl is also a RING finger ubiquitin ligase. Sawasdikosol S, Pratt JC, Meng W, Eck MJ, Burakoff SJ. Biochim Biophys Acta 1471 M1-M12 (2000)
  41. Ubiquitin ligases in malignant lymphoma. Lim MS, Elenitoba-Johnson KS. Leuk Lymphoma 45 1329-1339 (2004)
  42. Ubiquitin ligase Cbl-b and obesity-induced insulin resistance. Abe T, Hirasaka K, Kohno S, Ochi A, Yamagishi N, Ohno A, Teshima-Kondo S, Nikawa T. Endocr J 61 529-538 (2014)
  43. RTK SLAP down: the emerging role of Src-like adaptor protein as a key player in receptor tyrosine kinase signaling. Wybenga-Groot LE, McGlade CJ. Cell Signal 27 267-274 (2015)
  44. Cbl-family proteins as regulators of cytoskeleton-dependent phenomena. Lee H, Tsygankov AY. J Cell Physiol 228 2285-2293 (2013)
  45. Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance. Abe T, Hirasaka K, Nikawa T. World J Diabetes 8 97-103 (2017)
  46. Negative regulation of receptor tyrosine kinases by ubiquitination: Key roles of the Cbl family of E3 ubiquitin ligases. Tang R, Langdon WY, Zhang J. Front Endocrinol (Lausanne) 13 971162 (2022)
  47. E3 ubiquitin ligases in the acute leukemic signaling pathways. Zhan Q, Zhang H, Wu B, Zhang N, Zhang L. Front Physiol 13 1004330 (2022)
  48. Zooming into the structure-function of RING finger proteins for anti-cancer therapeutic applications. George M, Masamba P, Iwalokun BA, Kappo AP. Am J Cancer Res 13 2773-2789 (2023)

Articles citing this publication (124)

  1. The genome of the social amoeba Dictyostelium discoideum. Eichinger L, Pachebat JA, Glöckner G, Rajandream MA, Sucgang R, Berriman M, Song J, Olsen R, Szafranski K, Xu Q, Tunggal B, Kummerfeld S, Madera M, Konfortov BA, Rivero F, Bankier AT, Lehmann R, Hamlin N, Davies R, Gaudet P, Fey P, Pilcher K, Chen G, Saunders D, Sodergren E, Davis P, Kerhornou A, Nie X, Hall N, Anjard C, Hemphill L, Bason N, Farbrother P, Desany B, Just E, Morio T, Rost R, Churcher C, Cooper J, Haydock S, van Driessche N, Cronin A, Goodhead I, Muzny D, Mourier T, Pain A, Lu M, Harper D, Lindsay R, Hauser H, James K, Quiles M, Madan Babu M, Saito T, Buchrieser C, Wardroper A, Felder M, Thangavelu M, Johnson D, Knights A, Loulseged H, Mungall K, Oliver K, Price C, Quail MA, Urushihara H, Hernandez J, Rabbinowitsch E, Steffen D, Sanders M, Ma J, Kohara Y, Sharp S, Simmonds M, Spiegler S, Tivey A, Sugano S, White B, Walker D, Woodward J, Winckler T, Tanaka Y, Shaulsky G, Schleicher M, Weinstock G, Rosenthal A, Cox EC, Chisholm RL, Gibbs R, Loomis WF, Platzer M, Kay RR, Williams J, Dear PH, Noegel AA, Barrell B, Kuspa A. Nature 435 43-57 (2005)
  2. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Levkowitz G, Waterman H, Ettenberg SA, Katz M, Tsygankov AY, Alroy I, Lavi S, Iwai K, Reiss Y, Ciechanover A, Lipkowitz S, Yarden Y. Mol Cell 4 1029-1040 (1999)
  3. Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases. Zheng N, Wang P, Jeffrey PD, Pavletich NP. Cell 102 533-539 (2000)
  4. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W. Nat Cell Biol 4 222-231 (2002)
  5. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Pearson MA, Reczek D, Bretscher A, Karplus PA. Cell 101 259-270 (2000)
  6. Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Drum CL, Yan SZ, Bard J, Shen YQ, Lu D, Soelaiman S, Grabarek Z, Bohm A, Tang WJ. Nature 415 396-402 (2002)
  7. c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation. Naramura M, Jang IK, Kole H, Huang F, Haines D, Gu H. Nat Immunol 3 1192-1199 (2002)
  8. Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein. Peschard P, Fournier TM, Lamorte L, Naujokas MA, Band H, Langdon WY, Park M. Mol Cell 8 995-1004 (2001)
  9. The human and mouse complement of SH2 domain proteins-establishing the boundaries of phosphotyrosine signaling. Liu BA, Jablonowski K, Raina M, Arcé M, Pawson T, Nash PD. Mol Cell 22 851-868 (2006)
  10. Light-activated DNA binding in a designed allosteric protein. Strickland D, Moffat K, Sosnick TR. Proc Natl Acad Sci U S A 105 10709-10714 (2008)
  11. A logical model provides insights into T cell receptor signaling. Saez-Rodriguez J, Simeoni L, Lindquist JA, Hemenway R, Bommhardt U, Arndt B, Haus UU, Weismantel R, Gilles ED, Klamt S, Schraven B. PLoS Comput Biol 3 e163 (2007)
  12. Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation. Kurz T, Chou YC, Willems AR, Meyer-Schaller N, Hecht ML, Tyers M, Peter M, Sicheri F. Mol Cell 29 23-35 (2008)
  13. RING finger mutations that abolish c-Cbl-directed polyubiquitination and downregulation of the EGF receptor are insufficient for cell transformation. Thien CB, Walker F, Langdon WY. Mol Cell 7 355-365 (2001)
  14. Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl. Dou H, Buetow L, Hock A, Sibbet GJ, Vousden KH, Huang DT. Nat Struct Mol Biol 19 184-192 (2012)
  15. Regulation of protein tyrosine kinase signaling by substrate degradation during brain development. Arnaud L, Ballif BA, Cooper JA. Mol Cell Biol 23 9293-9302 (2003)
  16. Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading. Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29 4798-4811 (2009)
  17. Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases. Brdicka T, Kadlecek TA, Roose JP, Pastuszak AW, Weiss A. Mol Cell Biol 25 4924-4933 (2005)
  18. The non-receptor tyrosine kinase Syk is a target of Cbl-mediated ubiquitylation upon B-cell receptor stimulation. Rao N, Ghosh AK, Ota S, Zhou P, Reddi AL, Hakezi K, Druker BK, Wu J, Band H. EMBO J 20 7085-7095 (2001)
  19. The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. Hanke S, Mann M. Mol Cell Proteomics 8 519-534 (2009)
  20. Epidermal growth factor receptor internalization through clathrin-coated pits requires Cbl RING finger and proline-rich domains but not receptor polyubiquitylation. Jiang X, Sorkin A. Traffic 4 529-543 (2003)
  21. CBL is frequently altered in lung cancers: its relationship to mutations in MET and EGFR tyrosine kinases. Tan YH, Krishnaswamy S, Nandi S, Kanteti R, Vora S, Onel K, Hasina R, Lo FY, El-Hashani E, Cervantes G, Robinson M, Hsu HS, Kales SC, Lipkowitz S, Karrison T, Sattler M, Vokes EE, Wang YC, Salgia R. PLoS One 5 e8972 (2010)
  22. Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3. Dou H, Buetow L, Sibbet GJ, Cameron K, Huang DT. Nat Struct Mol Biol 20 982-986 (2013)
  23. The Cbl proto-oncogene product negatively regulates the Src-family tyrosine kinase Fyn by enhancing its degradation. Andoniou CE, Lill NL, Thien CB, Lupher ML, Ota S, Bowtell DD, Scaife RM, Langdon WY, Band H. Mol Cell Biol 20 851-867 (2000)
  24. Growth factor receptor binding protein 2-mediated recruitment of the RING domain of Cbl to the epidermal growth factor receptor is essential and sufficient to support receptor endocytosis. Huang F, Sorkin A. Mol Biol Cell 16 1268-1281 (2005)
  25. Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. Bullock AN, Rodriguez MC, Debreczeni JE, Songyang Z, Knapp S. Structure 15 1493-1504 (2007)
  26. APECED-causing mutations in AIRE reveal the functional domains of the protein. Halonen M, Kangas H, Rüppell T, Ilmarinen T, Ollila J, Kolmer M, Vihinen M, Palvimo J, Saarela J, Ulmanen I, Eskelin P. Hum Mutat 23 245-257 (2004)
  27. The linker phosphorylation site Tyr292 mediates the negative regulatory effect of Cbl on ZAP-70 in T cells. Rao N, Lupher ML, Ota S, Reedquist KA, Druker BJ, Band H. J Immunol 164 4616-4626 (2000)
  28. The phi29 DNA polymerase:protein-primer structure suggests a model for the initiation to elongation transition. Kamtekar S, Berman AJ, Wang J, Lázaro JM, de Vega M, Blanco L, Salas M, Steitz TA. EMBO J 25 1335-1343 (2006)
  29. TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Feshchenko EA, Smirnova EV, Swaminathan G, Teckchandani AM, Agrawal R, Band H, Zhang X, Annan RS, Carr SA, Tsygankov AY. Oncogene 23 4690-4706 (2004)
  30. Molecular mechanisms of ubiquitin-dependent membrane traffic. Hurley JH, Stenmark H. Annu Rev Biophys 40 119-142 (2011)
  31. Loops govern SH2 domain specificity by controlling access to binding pockets. Kaneko T, Huang H, Zhao B, Li L, Liu H, Voss CK, Wu C, Schiller MR, Li SS. Sci Signal 3 ra34 (2010)
  32. A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity. Hsu LY, Tan YX, Xiao Z, Malissen M, Weiss A. J Exp Med 206 2527-2541 (2009)
  33. C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in the receptor's carboxy-terminus. Wilhelmsen K, Burkhalter S, van der Geer P. Oncogene 21 1079-1089 (2002)
  34. Autoinhibition and phosphorylation-induced activation mechanisms of human cancer and autoimmune disease-related E3 protein Cbl-b. Kobashigawa Y, Tomitaka A, Kumeta H, Noda NN, Yamaguchi M, Inagaki F. Proc Natl Acad Sci U S A 108 20579-20584 (2011)
  35. Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding. Yasuda T, Maeda A, Kurosaki M, Tezuka T, Hironaka K, Yamamoto T, Kurosaki T. J Exp Med 191 641-650 (2000)
  36. SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling. Tang J, Sawasdikosol S, Chang JH, Burakoff SJ. Proc Natl Acad Sci U S A 96 9775-9780 (1999)
  37. Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins. Hu J, Hubbard SR. J Biol Chem 280 18943-18949 (2005)
  38. Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1. Mehlitz A, Banhart S, Mäurer AP, Kaushansky A, Gordus AG, Zielecki J, Macbeath G, Meyer TF. J Cell Biol 190 143-157 (2010)
  39. Loss of syk kinase during IgE-mediated stimulation of human basophils. Macglashan D, Miura K. J Allergy Clin Immunol 114 1317-1324 (2004)
  40. Constitutive endocytosis and degradation of the pre-T cell receptor. Panigada M, Porcellini S, Barbier E, Hoeflinger S, Cazenave PA, Gu H, Band H, von Boehmer H, Grassi F. J Exp Med 195 1585-1597 (2002)
  41. Cbl-mediated ubiquitinylation and negative regulation of Vav. Miura-Shimura Y, Duan L, Rao NL, Reddi AL, Shimura H, Rottapel R, Druker BJ, Tsygankov A, Band V, Band H. J Biol Chem 278 38495-38504 (2003)
  42. Negative regulation of EphA2 receptor by Cbl. Wang Yj, Ota S, Kataoka H, Kanamori M, Li Zy, Band H, Tanaka M, Sugimura H. Biochem Biophys Res Commun 296 214-220 (2002)
  43. T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase. Magnan A, Di Bartolo V, Mura AM, Boyer C, Richelme M, Lin YL, Roure A, Gillet A, Arrieumerlou C, Acuto O, Malissen B, Malissen M. J Exp Med 194 491-505 (2001)
  44. Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates. Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J. EMBO J 27 804-816 (2008)
  45. A mouse with a loss-of-function mutation in the c-Cbl TKB domain shows perturbed thymocyte signaling without enhancing the activity of the ZAP-70 tyrosine kinase. Thien CB, Scaife RM, Papadimitriou JM, Murphy MA, Bowtell DD, Langdon WY. J Exp Med 197 503-513 (2003)
  46. Combining multiple structure and sequence alignments to improve sequence detection and alignment: application to the SH2 domains of Janus kinases. Al-Lazikani B, Sheinerman FB, Honig B. Proc Natl Acad Sci U S A 98 14796-14801 (2001)
  47. A quantitative study of the recruitment potential of all intracellular tyrosine residues on EGFR, FGFR1 and IGF1R. Kaushansky A, Gordus A, Chang B, Rush J, MacBeath G. Mol Biosyst 4 643-653 (2008)
  48. Comparative genomic organization of the cbl genes. Nau MM, Lipkowitz S. Gene 308 103-113 (2003)
  49. Phosphotyrosine recognition domains: the typical, the atypical and the versatile. Kaneko T, Joshi R, Feller SM, Li SS. Cell Commun Signal 10 32 (2012)
  50. Ubiquitin ligase activity of c-Cbl guides the epidermal growth factor receptor into clathrin-coated pits by two distinct modes of Eps15 recruitment. de Melker AA, van der Horst G, Borst J. J Biol Chem 279 55465-55473 (2004)
  51. Cbl-3-deficient mice exhibit normal epithelial development. Griffiths EK, Sanchez O, Mill P, Krawczyk C, Hojilla CV, Rubin E, Nau MM, Khokha R, Lipkowitz S, Hui CC, Penninger JM. Mol Cell Biol 23 7708-7718 (2003)
  52. Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells. Yasuda T, Tezuka T, Maeda A, Inazu T, Yamanashi Y, Gu H, Kurosaki T, Yamamoto T. J Exp Med 196 51-63 (2002)
  53. Control of TCR-mediated activation of beta 1 integrins by the ZAP-70 tyrosine kinase interdomain B region and the linker for activation of T cells adapter protein. Goda S, Quale AC, Woods ML, Felthauser A, Shimizu Y. J Immunol 172 5379-5387 (2004)
  54. Identification of natural ligands for SH2 domains from a phage display cDNA library. Cochrane D, Webster C, Masih G, McCafferty J. J Mol Biol 297 89-97 (2000)
  55. Mutant Cbl proteins as oncogenic drivers in myeloproliferative disorders. Naramura M, Nadeau S, Mohapatra B, Ahmad G, Mukhopadhyay C, Sattler M, Raja SM, Natarajan A, Band V, Band H. Oncotarget 2 245-250 (2011)
  56. Ubiquitination switches EphA2 vesicular traffic from a continuous safeguard to a finite signalling mode. Sabet O, Stockert R, Xouri G, Brüggemann Y, Stanoev A, Bastiaens PIH. Nat Commun 6 8047 (2015)
  57. Functional cooperation between c-Cbl and Src-like adaptor protein 2 in the negative regulation of T-cell receptor signaling. Loreto MP, Berry DM, McGlade CJ. Mol Cell Biol 22 4241-4255 (2002)
  58. c-Cbl interacts with CD38 and promotes retinoic acid-induced differentiation and G0 arrest of human myeloblastic leukemia cells. Shen M, Yen A. Cancer Res 68 8761-8769 (2008)
  59. cbl-b inhibits EGF-receptor-induced apoptosis by enhancing ubiquitination and degradation of activated receptors. Ettenberg SA, Rubinstein YR, Banerjee P, Nau MM, Keane MM, Lipkowitz S. Mol Cell Biol Res Commun 2 111-118 (1999)
  60. c-Cbl inhibition improves cardiac function and survival in response to myocardial ischemia. Rafiq K, Kolpakov MA, Seqqat R, Guo J, Guo X, Qi Z, Yu D, Mohapatra B, Zutshi N, An W, Band H, Sanjay A, Houser SR, Sabri A. Circulation 129 2031-2043 (2014)
  61. A carboxyl-terminal hydrophobic interface is critical to sodium channel function. Relevance to inherited disorders. Glaaser IW, Bankston JR, Liu H, Tateyama M, Kass RS. J Biol Chem 281 24015-24023 (2006)
  62. c-Cbl ubiquitin ligase regulates focal adhesion protein turnover and myofibril degeneration induced by neutrophil protease cathepsin G. Rafiq K, Guo J, Vlasenko L, Guo X, Kolpakov MA, Sanjay A, Houser SR, Sabri A. J Biol Chem 287 5327-5339 (2012)
  63. Sequence, structure and energetic determinants of phosphopeptide selectivity of SH2 domains. Sheinerman FB, Al-Lazikani B, Honig B. J Mol Biol 334 823-841 (2003)
  64. The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme. Ryan PE, Sivadasan-Nair N, Nau MM, Nicholas S, Lipkowitz S. J Biol Chem 285 23687-23698 (2010)
  65. Requirement for tyrosine residues 315 and 319 within zeta chain-associated protein 70 for T cell development. Gong Q, Jin X, Akk AM, Foger N, White M, Gong G, Bubeck Wardenburg J, Chan AC. J Exp Med 194 507-518 (2001)
  66. Binding specificity of SH2 domains: insight from free energy simulations. Gan W, Roux B. Proteins 74 996-1007 (2009)
  67. Platelet alpha IIb-beta 3 integrin engagement induces the tyrosine phosphorylation of Cbl and its association with phosphoinositide 3-kinase and Syk. Saci A, Rendu F, Bachelot-Loza C. Biochem J 351 Pt 3 669-676 (2000)
  68. YXXM motifs in the PDGF-beta receptor serve dual roles as phosphoinositide 3-kinase binding motifs and tyrosine-based endocytic sorting signals. Wu H, Windmiller DA, Wang L, Backer JM. J Biol Chem 278 40425-40428 (2003)
  69. Identification of the linker-SH2 domain of STAT as the origin of the SH2 domain using two-dimensional structural alignment. Gao Q, Hua J, Kimura R, Headd JJ, Fu XY, Chin YE. Mol Cell Proteomics 3 704-714 (2004)
  70. Regulation of Cbl phosphorylation by the Abl tyrosine kinase and the Nck SH2/SH3 adaptor. Miyoshi-Akiyama T, Aleman LM, Smith JM, Adler CE, Mayer BJ. Oncogene 20 4058-4069 (2001)
  71. Requirements of multiple domains of SLI-1, a Caenorhabditis elegans homologue of c-Cbl, and an inhibitory tyrosine in LET-23 in regulating vulval differentiation. Yoon CH, Chang C, Hopper NA, Lesa GM, Sternberg PW. Mol Biol Cell 11 4019-4031 (2000)
  72. Cbl-transforming variants trigger a cascade of molecular alterations that lead to epithelial mesenchymal conversion. Fournier TM, Lamorte L, Maroun CR, Lupher M, Band H, Langdon W, Park M. Mol Biol Cell 11 3397-3410 (2000)
  73. Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations. Martinelli S, Stellacci E, Pannone L, D'Agostino D, Consoli F, Lissewski C, Silvano M, Cencelli G, Lepri F, Maitz S, Pauli S, Rauch A, Zampino G, Selicorni A, Melançon S, Digilio MC, Gelb BD, De Luca A, Dallapiccola B, Zenker M, Tartaglia M. Hum Mutat 36 787-796 (2015)
  74. TCR/CD3 down-modulation and zeta degradation are regulated by ZAP-70. Dumont C, Blanchard N, Di Bartolo V, Lezot N, Dufour E, Jauliac S, Hivroz C. J Immunol 169 1705-1712 (2002)
  75. c-Cbl binds to tyrosine-phosphorylated neurotrophin receptor p75 and induces its ubiquitination. Ohrt T, Mancini A, Tamura T, Niedenthal R. Cell Signal 16 1291-1298 (2004)
  76. The Src-like adaptor protein 2 regulates colony-stimulating factor-1 receptor signaling and down-regulation. Pakuts B, Debonneville C, Liontos LM, Loreto MP, McGlade CJ. J Biol Chem 282 17953-17963 (2007)
  77. c-Cbl tyrosine kinase-binding domain mutant G306E abolishes the interaction of c-Cbl with CD38 and fails to promote retinoic acid-induced cell differentiation and G0 arrest. Shen M, Yen A. J Biol Chem 284 25664-25677 (2009)
  78. The proto-oncogene c-Cbl is a negative regulator of DNA synthesis initiated by both receptor and cytoplasmic tyrosine kinases. Broome MA, Galisteo ML, Schlessinger J, Courtneidge SA. Oncogene 18 2908-2912 (1999)
  79. c-Cbl is not required for ERK1/2-dependent degradation of BimEL. Wiggins CM, Band H, Cook SJ. Cell Signal 19 2605-2611 (2007)
  80. Identification and functional characterization of an Src homology domain 3 domain-binding site on Cbl. Sanjay A, Miyazaki T, Itzstein C, Purev E, Horne WC, Baron R. FEBS J 273 5442-5456 (2006)
  81. Isolation and characterization of a novel, transforming allele of the c-Cbl proto-oncogene from a murine macrophage cell line. Bisson SA, Ujack EE, Robbins SM. Oncogene 21 3677-3687 (2002)
  82. Stimulation of hERG1 channel activity promotes a calcium-dependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells. Perez-Neut M, Shum A, Cuevas BD, Miller R, Gentile S. Oncotarget 6 1631-1639 (2015)
  83. article-commentary Cbl exposes its RING finger. Kales SC, Ryan PE, Lipkowitz S. Nat Struct Mol Biol 19 131-133 (2012)
  84. Biochemical basis for the requirement of kinase activity for Cbl-dependent ubiquitinylation and degradation of a target tyrosine kinase. Ghosh AK, Reddi AL, Rao NL, Duan L, Band V, Band H. J Biol Chem 279 36132-36141 (2004)
  85. High-throughput fluorescence polarization assay to identify inhibitors of Cbl(TKB)-protein tyrosine kinase interactions. Kumar EA, Charvet CD, Lokesh GL, Natarajan A. Anal Biochem 411 254-260 (2011)
  86. LncRNA DUXAP9-206 directly binds with Cbl-b to augment EGFR signaling and promotes non-small cell lung cancer progression. Zhu T, An S, Choy MT, Zhou J, Wu S, Liu S, Liu B, Yao Z, Zhu X, Wu J, He Z. J Cell Mol Med 23 1852-1864 (2019)
  87. Selective inhibition of Fcepsilon RI-mediated mast cell activation by a truncated variant of Cbl-b related to the rat model of type 1 diabetes mellitus. Qu X, Miah SM, Hatani T, Okazaki M, Hori-Tamura N, Yamamura H, Hotta H, Sada K. J Biochem 137 711-720 (2005)
  88. The kinase-deficient Src acts as a suppressor of the Abl kinase for Cbl phosphorylation. Shishido T, Akagi T, Ouchi T, Georgescu MM, Langdon WY, Hanafusa H. Proc Natl Acad Sci U S A 97 6439-6444 (2000)
  89. Additional serine/threonine phosphorylation reduces binding affinity but preserves interface topography of substrate proteins to the c-Cbl TKB domain. Sun Q, Jackson RA, Ng C, Guy GR, Sivaraman J. PLoS One 5 e12819 (2010)
  90. The oncogenic 70Z Cbl mutation blocks the phosphotyrosine binding domain-dependent negative regulation of ZAP-70 by c-Cbl in Jurkat T cells. van Leeuwen JE, Paik PK, Samelson LE. Mol Cell Biol 19 6652-6664 (1999)
  91. Oncogenic Signaling by Leukemia-Associated Mutant Cbl Proteins. Nadeau S, An W, Palermo N, Feng D, Ahmad G, Dong L, Borgstahl GE, Natarajan A, Naramura M, Band V, Band H. Biochem Anal Biochem Suppl 6 7921 (2012)
  92. The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules. Teckchandani AM, Birukova AA, Tar K, Verin AD, Tsygankov AY. Exp Cell Res 306 114-127 (2005)
  93. c-Cbl regulates migration of v-Abl-transformed NIH 3T3 fibroblasts via Rac1. Teckchandani AM, Panetti TS, Tsygankov AY. Exp Cell Res 307 247-258 (2005)
  94. An essential role of ubiquitination in Cbl-mediated negative regulation of the Src-family kinase Fyn. Rao N, Ghosh AK, Douillard P, Andoniou CE, Zhou P, Band H. Signal Transduct 2 29-39 (2002)
  95. Cbl-family ubiquitin ligases and their recruitment of CIN85 are largely dispensable for epidermal growth factor receptor endocytosis. Ahmad G, Mohapatra BC, Schulte NA, Nadeau SA, Luan H, Zutshi N, Tom E, Ortega-Cava C, Tu C, Sanada M, Ogawa S, Toews ML, Band V, Band H. Int J Biochem Cell Biol 57 123-134 (2014)
  96. Peptide truncation leads to a twist and an unusual increase in affinity for casitas B-lineage lymphoma tyrosine kinase binding domain. Kumar EA, Yuan Z, Palermo NY, Dong L, Ahmad G, Lokesh GL, Kolar C, Kizhake S, Borgstahl GE, Band H, Natarajan A. J Med Chem 55 3583-3587 (2012)
  97. The Cbl RING finger C-terminal flank controls epidermal growth factor receptor fate downstream of receptor ubiquitination. Visser GD, Lill NL. Exp Cell Res 311 281-293 (2005)
  98. The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides. Kumar EA, Chen Q, Kizhake S, Kolar C, Kang M, Chang CE, Borgstahl GE, Natarajan A. Sci Rep 3 1639 (2013)
  99. Comment An SH2 domain in disguise. Kuriyan J, Darnell JE. Nature 398 22-3, 25 (1999)
  100. CD43 regulates the threshold for T cell activation by targeting Cbl functions. Pedraza-Alva G, Mérida LB, del Rio R, Fierro NA, Cruz-Muñoz ME, Olivares N, Melchy E, Igras V, Holländer GA, Burakoff SJ, Rosenstein Y. IUBMB Life 63 940-948 (2011)
  101. Cbl-mediated K63-linked ubiquitination of JAK2 enhances JAK2 phosphorylation and signal transduction. Liu CS, Yang-Yen HF, Suen CS, Hwang MJ, Yen JJ. Sci Rep 7 4613 (2017)
  102. JAK-cytokine receptor recognition, unboxed. McNally R, Eck MJ. Nat Struct Mol Biol 21 431-433 (2014)
  103. SLI-1 Cbl inhibits the engulfment of apoptotic cells in C. elegans through a ligase-independent function. Anderson C, Zhou S, Sawin E, Horvitz HR, Hurwitz ME. PLoS Genet 8 e1003115 (2012)
  104. Structural differences among subfamilies of EF-hand proteins--a view from the pseudo two-fold symmetry axis. Kawasaki H, Kretsinger RH. Proteins 82 2915-2924 (2014)
  105. Calmodulin regulates MGRN1-GP78 interaction mediated ubiquitin proteasomal degradation system. Mukherjee R, Bhattacharya A, Sau A, Basu S, Chakrabarti S, Chakrabarti O. FASEB J 33 1927-1945 (2019)
  106. PH domains in WASP - a bug in the system? reply Miki H, Takenawa T. Trends Cell Biol 9 212 (1999)
  107. Tyrosine 315 determines optimal recruitment of ZAP-70 to the T cell antigen receptor. Di Bartolo V, Malissen M, Dufour E, Sechet E, Malissen B, Acuto O. Eur J Immunol 32 568-575 (2002)
  108. Casitas B-cell lymphoma (Cbl) proteins protect mammary epithelial cells from proteotoxicity of active c-Src accumulation. Mukhopadhyay C, Triplett A, Bargar T, Heckman C, Wagner KU, Naramura M. Proc Natl Acad Sci U S A 113 E8228-E8237 (2016)
  109. Coexistence of phosphotyrosine-dependent and -independent interactions between Cbl and Bcr-Abl. Gaston I, Johnson KJ, Oda T, Bhat A, Reis M, Langdon W, Shen L, Deininger MW, Druker BJ. Exp Hematol 32 113-121 (2004)
  110. Latent dynamics of a protein molecule observed in dihedral angle space. Omori S, Fuchigami S, Ikeguchi M, Kidera A. J Chem Phys 132 115103 (2010)
  111. Biodegradable and Excretable 2D W1.33 C i-MXene with Vacancy Ordering for Theory-Oriented Cancer Nanotheranostics in Near-Infrared Biowindow. Zhou B, Yin H, Dong C, Sun L, Feng W, Pu Y, Han X, Li X, Du D, Xu H, Chen Y. Adv Sci (Weinh) 8 e2101043 (2021)
  112. ErbB2 and ErbB4 Cbl binding sites can functionally replace the ErbB1 Cbl binding site. Jansen SM, Sleumer LS, Damen E, Meijer IM, van Zoelen EJ, van Leeuwen JE. Cell Signal 21 810-818 (2009)
  113. The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation. Lin H, Martelli MP, Bierer BE. Int Immunol 13 13-22 (2001)
  114. A PKC-SHP1 signaling axis desensitizes Fcγ receptor signaling by reducing the tyrosine phosphorylation of CBL and regulates FcγR mediated phagocytosis. Joshi S, Singh AR, Zulcic M, Durden DL. BMC Immunol 15 18 (2014)
  115. Critical role of Ser-520 phosphorylation for membrane recruitment and activation of the ZAP-70 tyrosine kinase in T cells. Yang Y, Villain P, Mustelin T, Couture C. Mol Cell Biol 23 7667-7677 (2003)
  116. Spred-2 steady-state levels are regulated by phosphorylation and Cbl-mediated ubiquitination. Lock P, I ST, Straffon AF, Schieb H, Hovens CM, Stylli SS. Biochem Biophys Res Commun 351 1018-1023 (2006)
  117. Incidence of c-Cbl mutations in human acute myeloid leukaemias in an Australian patient cohort. Ghassemifar R, Thien CB, Finlayson J, Joske D, Cull GM, Augustson B, Langdon WY. Pathology 43 261-265 (2011)
  118. Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c. Takeshita K, Tezuka T, Isozaki Y, Yamashita E, Suzuki M, Kim M, Yamanashi Y, Yamamoto T, Nakagawa A. J Biochem 152 487-495 (2012)
  119. Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues. Mercurio FA, Marasco D, Di Natale C, Pirone L, Costantini S, Pedone EM, Leone M. Chembiochem 17 2179-2188 (2016)
  120. Characterization of the mouse Cblc/Cbl3 gene. Fiore F, Ollendorff V, Birnbaum D. Biochem Biophys Res Commun 280 182-187 (2001)
  121. Expression and Comparison of Cbl-b in Lung Squamous Cell Carcinoma and Adenocarcinoma. Li P, Liu H, Zhang Z, Lv X, Wang H, Ma J, Ma Z, Qu X, Teng YE. Med Sci Monit 24 623-635 (2018)
  122. Role of the Src homology 2 domains and interdomain regions in ZAP-70 phosphorylation and enzymatic activity. Magistrelli G, Bosotti R, Valsasina B, Visco C, Perego R, Toma S, Acuto O, Isacchi A. Eur J Biochem 266 1166-1173 (1999)
  123. Letter c-Cbl inhibition: A novel therapeutic approach for attenuating myocardial ischemia and reperfusion injury. Wang J, Li L, Jiang H. Int J Cardiol 186 50-51 (2015)
  124. The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition. Kimani SW, Perveen S, Szewezyk M, Zeng H, Dong A, Li F, Ghiabi P, Li Y, Chau I, Arrowsmith CH, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Halabelian L. Commun Biol 6 1272 (2023)


Quick links