Cbl proto-oncogene, E3 ubiquitin protein ligase |

PDB rendering based on 1b47. |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1B47, 1FBV, 1YVH, 2CBL, 2JUJ, 2K4D, 2OO9, 2Y1M, 2Y1N, 3BUM, 3BUN, 3BUO, 3BUW, 3BUX, 3OB1, 3OB2, 3PLF, 4A49, 4A4B, 4A4C
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Identifiers |
Symbols |
CBL; C-CBL; CBL2; NSLL; RNF55 |
External IDs |
OMIM: 165360 MGI: 88279 HomoloGene: 3802 GeneCards: CBL Gene |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
867 |
12402 |
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Ensembl |
ENSG00000110395 |
ENSMUSG00000034342 |
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UniProt |
P22681 |
P22682 |
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RefSeq (mRNA) |
NM_005188.3 |
NM_007619.2 |
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RefSeq (protein) |
NP_005179.2 |
NP_031645.2 |
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Location (UCSC) |
Chr 11:
119.08 – 119.18 Mb |
Chr 9:
43.96 – 44.04 Mb |
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PubMed search |
[1] |
[2] |
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Cbl (named after Casitas B-lineage Lymphoma) is a mammalian gene encoding several proteins including E3 ubiquitin-protein ligase CBL involved in cell signalling and protein ubiquitination. Mutations to this gene have been implication in a number of human cancers, particularly acute myeloid leukaemia.
In 1989 a virally encoded portion of the chromosomal mouse Cbl gene was the first member of the Cbl family to be discovered[1] and was named v-Cbl to distinguish it from normal mouse c-Cbl. The virus used in the experiment was a retrovirus known as Cas-Br-M, and was found to have excised approximately a third of the original c-Cbl gene from mice it was injected into. Sequencing revealed that the portion carried by the retrovirus encoded a tyrosine kinase binding domain, and that this was the oncogenic form as retroviruses carrying full-length c-Cbl did not induce tumour formation. The resultant transformed retrovirus was found to consistently induce a type of pre-B lymphoma, known as Casitas B-lineage lymphoma, in infected mice.
Full length c-Cbl has been found to consist of several regions encoding for functionally distinct protein domains:
This domain structure and the tyrosine and serine-rich content of the protein product is typical of an "adaptor molecule" used in cell signalling pathways.[2]
Three mammalian homologues have been characterized, which all differ in their ability to function as adaptor proteins due to the differing lengths of their C-terminal UBA domains:
- c-Cbl: ubiquitously expressed, 906 amino acids in length.
- Cbl-b: ubiquitously expressed, 982 amino acids long in length.
- Cbl-c: lacks the UBA domain and is therefore only 474 amino acids in length. It is primarily expressed in epithelial cells however its function is poorly understood.
Interestingly, both c-Cbl and Cbl-b have orthologues in D. melanogaster (D-Cbl) and C. elegans (Sli-1), hinting at a long evolutionary path for these proteins.[2]
Ubiquitination is the process of chemically attaching ubiquitin monomers to a protein, thereby targeting it for degradation. As this is a multi-step process, several different enzymes are involved, the final one being a member of the E3 family of ligases. Cbl functions as an E3 ligase, and therefore is able to catalyse the formation of a covalent bond between ubiquitin and Cbl's protein substrate - typically a receptor tyrosine kinase. The RING-finger domain mediates this transfer, however like other E3 ligases of the RING type no intermediate covalent bond is formed between ubiquitin and the RING-finger domain. The stepwise attachment of ubiquitin to the substrate receptor tyrosine kinase can lead to its removal from the plasma membrane and subsequent trafficking to the lysosome for degradation.
Cbl gene has been shown to interact with:
- Abl gene,[3][4]
- ARHGEF7,[5]
- C-Met,[6][7]
- CD2AP,[8][9][10]
- CSF1R.[11]
- CRK,[12][13]
- CRKL,[14][15][16][17][18][19][20][21]
- EGFR,[6]<[22][23]
- FRS2,[24]
- FYN,[18][25]
- Grb2,[6][12][13][14][24][26][27][28][29][30][31][32][33]
- HCK,[34][35]
- IGF1R,[36]
- LCP2;,[14][37]
- NCK1,[3][14]
- PDGFRA,[38]
- PIK3R1,[12][39][40]
- PIK3R2,[15][41]
- PLCG1,[22][42]
- PTK2B,[8][43]
- PTPN11,[44]
- SH2B2,[6][45]
- SH3KBP1[7][46][47][48][49]
- SHC1,[12][26]
- SLA2,[50]
- SORBS1,[8][51]
- SORBS2,[4][8]
- SPRY2,[6][52][53]
- Syk,[54][55][56]
- UBE2L3,[52][57][58]
- VAV1,[55][59]
- YWHAB,[30]
- YWHAQ,[60][61] and
- ZAP-70,[62][63]
- ^ Langdon WY, Hartley JW, Klinken SP, Ruscetti SK, Morse HC (1989). "v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas". Proc. Natl. Acad. Sci. U.S.A. 86 (4): 1168–72. DOI:10.1073/pnas.86.4.1168. PMC 286647. PMID 2784003. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=286647.
- ^ a b Schmidt MH, Dikic I (2005). "The Cbl interactome and its functions". Nat. Rev. Mol. Cell Biol. 6 (12): 907–18. DOI:10.1038/nrm1762. PMID 16227975.
- ^ a b Miyoshi-Akiyama, T; Aleman L M, Smith J M, Adler C E, Mayer B J (July 2001). "Regulation of Cbl phosphorylation by the Abl tyrosine kinase and the Nck SH2/SH3 adaptor". Oncogene (England) 20 (30): 4058–69. DOI:10.1038/sj.onc.1204528. ISSN 0950-9232. PMID 11494134.
- ^ a b Soubeyran P, Barac A, Szymkiewicz I, Dikic I (February 2003). "Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl". Biochem. J. 370 (Pt 1): 29–34. DOI:10.1042/BJ20021539. PMC 1223168. PMID 12475393. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223168.
- ^ Flanders JA, Feng Q, Bagrodia S, Laux MT, Singavarapu A, Cerione RA (August 2003). "The Cbl proteins are binding partners for the Cool/Pix family of p21-activated kinase-binding proteins". FEBS Lett. 550 (1-3): 119–23. DOI:10.1016/S0014-5793(03)00853-6. PMID 12935897.
- ^ a b c d e Ng, Cherlyn; Jackson Rebecca A, Buschdorf Jan P, Sun Qingxiang, Guy Graeme R, Sivaraman J (March 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. (England) 27 (5): 804–16. DOI:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2265755.
- ^ a b Petrelli A, Gilestro GF, Lanzardo S, Comoglio PM, Migone N, Giordano S (March 2002). "The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met". Nature 416 (6877): 187–90. DOI:10.1038/416187a. PMID 11894096.
- ^ a b c d Haglund, Kaisa; Ivankovic-Dikic Inga, Shimokawa Noriaki, Kruh Gary D, Dikic Ivan (May. 2004). "Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites". J. Cell. Sci. (England) 117 (Pt 12): 2557–68. DOI:10.1242/jcs.01148. ISSN 0021-9533. PMID 15128873.
- ^ Kirsch KH, Georgescu MM, Shishido T, Langdon WY, Birge RB, Hanafusa H (February 2001). "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction". J. Biol. Chem. 276 (7): 4957–63. DOI:10.1074/jbc.M005784200. PMID 11067845.
- ^ Cormont, Mireille; Metón Isidoro, Mari Muriel, Monzo Pascale, Keslair Frédérique, Gaskin Chantell, McGraw Timothy E, Le Marchand-Brustel Yannick (February 2003). "CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl". Traffic (Denmark) 4 (2): 97–112. DOI:10.1034/j.1600-0854.2003.40205.x. ISSN 1398-9219. PMID 12559036.
- ^ Mancini A, Koch A, Wilms R, Tamura T (April 2002). "c-Cbl associates directly with the C-terminal tail of the receptor for the macrophage colony-stimulating factor, c-Fms, and down-modulates this receptor but not the viral oncogene v-Fms". J. Biol. Chem. 277 (17): 14635–40. DOI:10.1074/jbc.M109214200. PMID 11847211.
- ^ a b c d Gesbert, F; Garbay C, Bertoglio J (February 1998). "Interleukin-2 stimulation induces tyrosine phosphorylation of p120-Cbl and CrkL and formation of multimolecular signaling complexes in T lymphocytes and natural killer cells". J. Biol. Chem. (UNITED STATES) 273 (7): 3986–93. DOI:10.1074/jbc.273.7.3986. ISSN 0021-9258. PMID 9461587.
- ^ a b Husson H, Mograbi B, Schmid-Antomarchi H, Fischer S, Rossi B (May 1997). "CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2". Oncogene 14 (19): 2331–8. DOI:10.1038/sj.onc.1201074. PMID 9178909.
- ^ a b c d Erdreich-Epstein, A; Liu M, Kant A M, Izadi K D, Nolta J A, Durden D L (April 1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. (UNITED STATES) 65 (4): 523–34. ISSN 0741-5400. PMID 10204582.
- ^ a b Lin H, Martelli MP, Bierer BE (January 2001). "The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation". Int. Immunol. 13 (1): 13–22. DOI:10.1093/intimm/13.1.13. PMID 11133830.
- ^ Kyono WT, de Jong R, Park RK, Liu Y, Heisterkamp N, Groffen J, Durden DL (November 1998). "Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI)". J. Immunol. 161 (10): 5555–63. PMID 9820532.
- ^ Park RK, Kyono WT, Liu Y, Durden DL (May 1998). "CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif signaling". J. Immunol. 160 (10): 5018–27. PMID 9590251.
- ^ a b Taher TE, Tjin EP, Beuling EA, Borst J, Spaargaren M, Pals ST (October 2002). "c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination". J. Immunol. 169 (7): 3793–800. PMID 12244174.
- ^ Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD (April 1997). "Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)". J. Biol. Chem. 272 (15): 10248–53. DOI:10.1074/jbc.272.15.10248. PMID 9092574.
- ^ Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, Golemis EA, Griffin JD (May 1997). "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". J. Biol. Chem. 272 (22): 14320–6. DOI:10.1074/jbc.272.22.14320. PMID 9162067.
- ^ Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O (October 1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochem. Biophys. Res. Commun. 239 (2): 412–7. DOI:10.1006/bbrc.1997.7480. PMID 9344843.
- ^ a b Tvorogov D, Carpenter G (July 2002). "EGF-dependent association of phospholipase C-gamma1 with c-Cbl". Exp. Cell Res. 277 (1): 86–94. DOI:10.1006/excr.2002.5545. PMID 12061819.
- ^ Umebayashi K, Stenmark H, Yoshimori T (August 2008). "Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation". Mol. Biol. Cell 19 (8): 3454–62. DOI:10.1091/mbc.E07-10-0988. PMC 2488299. PMID 18508924. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2488299.
- ^ a b Wong, Andy; Lamothe Betty, Lee Arnold, Schlessinger Joseph, Lax Irit, Li Arnold (May. 2002). "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (10): 6684–9. DOI:10.1073/pnas.052138899. ISSN 0027-8424. PMC 124463. PMID 11997436. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=124463.
- ^ Deckert M, Elly C, Altman A, Liu YC (April 1998). "Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases". J. Biol. Chem. 273 (15): 8867–74. DOI:10.1074/jbc.273.15.8867. PMID 9535867.
- ^ a b Park, R K; Erdreich-Epstein A, Liu M, Izadi K D, Durden D L (December 1999). "High affinity IgG receptor activation of Src family kinases is required for modulation of the Shc-Grb2-Sos complex and the downstream activation of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase". J. Immunol. (UNITED STATES) 163 (11): 6023–34. ISSN 0022-1767. PMID 10570290.
- ^ Jain, S K; Langdon W Y, Varticovski L (May. 1997). "Tyrosine phosphorylation of p120cbl in BCR/abl transformed hematopoietic cells mediates enhanced association with phosphatidylinositol 3-kinase". Oncogene (ENGLAND) 14 (18): 2217–28. DOI:10.1038/sj.onc.1201049. ISSN 0950-9232. PMID 9174058.
- ^ Liu, S K; McGlade C J (December 1998). "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc". Oncogene (ENGLAND) 17 (24): 3073–82. DOI:10.1038/sj.onc.1202337. ISSN 0950-9232. PMID 9872323.
- ^ Ettenberg, S A; Keane M M, Nau M M, Frankel M, Wang L M, Pierce J H, Lipkowitz S (March 1999). "cbl-b inhibits epidermal growth factor receptor signaling". Oncogene (ENGLAND) 18 (10): 1855–66. DOI:10.1038/sj.onc.1202499. ISSN 0950-9232. PMID 10086340.
- ^ a b Robertson, H; Langdon W Y, Thien C B, Bowtell D D (November 1997). "A c-Cbl yeast two hybrid screen reveals interactions with 14-3-3 isoforms and cytoskeletal components". Biochem. Biophys. Res. Commun. (UNITED STATES) 240 (1): 46–50. DOI:10.1006/bbrc.1997.7608. ISSN 0006-291X. PMID 9367879.
- ^ Donovan, J A; Wange R L, Langdon W Y, Samelson L E (September 1994). "The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor". J. Biol. Chem. (UNITED STATES) 269 (37): 22921–4. ISSN 0021-9258. PMID 8083187.
- ^ Saci, Abdelhafid; Liu Wang-Qing, Vidal Michel, Garbay Christiane, Rendu Francine, Bachelot-Loza Christilla (May. 2002). "Differential effect of the inhibition of Grb2-SH3 interactions in platelet activation induced by thrombin and by Fc receptor engagement". Biochem. J. (England) 363 (Pt 3): 717–25. DOI:10.1042/0264-6021:3630717. ISSN 0264-6021. PMC 1222524. PMID 11964172. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1222524.
- ^ Odai, H; Sasaki K, Iwamatsu A, Nakamoto T, Ueno H, Yamagata T, Mitani K, Yazaki Y, Hirai H (April 1997). "Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl". Blood (UNITED STATES) 89 (8): 2745–56. ISSN 0006-4971. PMID 9108392.
- ^ Howlett, Christopher J; Robbins Stephen M (March 2002). "Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated cellular transformation". Oncogene (England) 21 (11): 1707–16. DOI:10.1038/sj.onc.1205228. ISSN 0950-9232. PMID 11896602.
- ^ Howlett, C J; Bisson S A, Resek M E, Tigley A W, Robbins S M (April 1999). "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase". Biochem. Biophys. Res. Commun. (UNITED STATES) 257 (1): 129–38. DOI:10.1006/bbrc.1999.0427. ISSN 0006-291X. PMID 10092522.
- ^ Sehat, Bita; Andersson Sandra, Girnita Leonard, Larsson Olle (July 2008). "Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis". Cancer Res. (United States) 68 (14): 5669–77. DOI:10.1158/0008-5472.CAN-07-6364. PMID 18632619.
- ^ Park, R K; Izadi K D, Deo Y M, Durden D L (September 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling". Blood (UNITED STATES) 94 (6): 2112–20. ISSN 0006-4971. PMID 10477741.
- ^ Bonita, D P; Miyake S, Lupher M L, Langdon W Y, Band H (August 1997). "Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity". Mol. Cell. Biol. (UNITED STATES) 17 (8): 4597–610. ISSN 0270-7306. PMC 232313. PMID 9234717. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232313.
- ^ Zhang, S; Broxmeyer H E (January 1999). "p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2, SHIP, and a tyrosine-phosphorylated 100-kDa protein in Flt3 ligand-stimulated hematopoietic cells". Biochem. Biophys. Res. Commun. (UNITED STATES) 254 (2): 440–5. DOI:10.1006/bbrc.1998.9959. ISSN 0006-291X. PMID 9918857.
- ^ Dufour, Cécilie; Guenou Hind, Kaabeche Karim, Bouvard Daniel, Sanjay Archana, Marie Pierre J (June 2008). "FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival". Bone (United States) 42 (6): 1032–9. DOI:10.1016/j.bone.2008.02.009. ISSN 8756-3282. PMID 18374639.
- ^ Hartley, D; Meisner H, Corvera S (August 1995). "Specific association of the beta isoform of the p85 subunit of phosphatidylinositol-3 kinase with the proto-oncogene c-cbl". J. Biol. Chem. (UNITED STATES) 270 (31): 18260–3. DOI:10.1074/jbc.270.31.18260. ISSN 0021-9258. PMID 7629144.
- ^ Graham, L J; Stoica B A, Shapiro M, DeBell K E, Rellahan B, Laborda J, Bonvini E (August 1998). "Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl". Biochem. Biophys. Res. Commun. (UNITED STATES) 249 (2): 537–41. DOI:10.1006/bbrc.1998.9177. ISSN 0006-291X. PMID 9712732.
- ^ Sanjay, A; Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne W C, Baron R (January 2001). "Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility". J. Cell Biol. (United States) 152 (1): 181–95. DOI:10.1083/jcb.152.1.181. ISSN 0021-9525. PMC 2193648. PMID 11149930. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2193648.
- ^ Tanaka, Yoshinori; Tanaka Nobuyuki, Saeki Yasushi, Tanaka Keiji, Murakami Masaaki, Hirano Toshio, Ishii Naoto, Sugamura Kazuo (August 2008). "c-Cbl-dependent monoubiquitination and lysosomal degradation of gp130". Mol. Cell. Biol. (United States) 28 (15): 4805–18. DOI:10.1128/MCB.01784-07. PMC 2493370. PMID 18519587. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2493370.
- ^ Wakioka, T; Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A (May. 1999). "APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl". Leukemia (ENGLAND) 13 (5): 760–7. DOI:10.1038/sj/leu/2401397. ISSN 0887-6924. PMID 10374881.
- ^ Watanabe, S; Take H, Takeda K, Yu Z X, Iwata N, Kajigaya S (November 2000). "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochem. Biophys. Res. Commun. (UNITED STATES) 278 (1): 167–74. DOI:10.1006/bbrc.2000.3760. ISSN 0006-291X. PMID 11071869.
- ^ Soubeyran, Philippe; Kowanetz Katarzyna, Szymkiewicz Iwona, Langdon Wallace Y, Dikic Ivan (March 2002). "Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors". Nature (England) 416 (6877): 183–7. DOI:10.1038/416183a. ISSN 0028-0836. PMID 11894095.
- ^ Szymkiewicz, Iwona; Kowanetz Katarzyna, Soubeyran Philippe, Dinarina Ana, Lipkowitz Stanley, Dikic Ivan (October 2002). "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases". J. Biol. Chem. (United States) 277 (42): 39666–72. DOI:10.1074/jbc.M205535200. ISSN 0021-9258. PMID 12177062.
- ^ Borinstein, S C; Hyatt M A, Sykes V W, Straub R E, Lipkowitz S, Boulter J, Bogler O (December 2000). "SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins". Cell. Signal. (ENGLAND) 12 (11-12): 769–79. DOI:10.1016/S0898-6568(00)00129-7. ISSN 0898-6568. PMID 11152963.
- ^ Pandey, Akhilesh; Ibarrola Nieves, Kratchmarova Irina, Fernandez Minerva M, Constantinescu Stefan N, Ohara Osamu, Sawasdikosol Sansana, Lodish Harvey F, Mann Matthias (May. 2002). "A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell receptor signaling". J. Biol. Chem. (United States) 277 (21): 19131–8. DOI:10.1074/jbc.M110318200. ISSN 0021-9258. PMID 11891219.
- ^ Vandenbroere, Isabelle; Paternotte Nathalie, Dumont Jacques E, Erneux Christophe, Pirson Isabelle (January 2003). "The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing inositol polyphosphate 5-phosphatase SHIP2". Biochem. Biophys. Res. Commun. (United States) 300 (2): 494–500. DOI:10.1016/S0006-291X(02)02894-2. ISSN 0006-291X. PMID 12504111.
- ^ a b Wong, Esther Sook Miin; Fong Chee Wai, Lim Jormay, Yusoff Permeen, Low Boon Chuan, Langdon Wallace Y, Guy Graeme R (September 2002). "Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling". EMBO J. (England) 21 (18): 4796–808. DOI:10.1093/emboj/cdf493. ISSN 0261-4189. PMC 126289. PMID 12234920. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=126289.
- ^ Wong, E S; Lim J, Low B C, Chen Q, Guy G R (February 2001). "Evidence for direct interaction between Sprouty and Cbl". J. Biol. Chem. (United States) 276 (8): 5866–75. DOI:10.1074/jbc.M006945200. ISSN 0021-9258. PMID 11053437.
- ^ Lupher, M L; Rao N, Lill N L, Andoniou C E, Miyake S, Clark E A, Druker B, Band H (December 1998). "Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323". J. Biol. Chem. (UNITED STATES) 273 (52): 35273–81. DOI:10.1074/jbc.273.52.35273. ISSN 0021-9258. PMID 9857068.
- ^ a b Bertagnolo, V; Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi M L, Capitani S (April 2001). "Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells". Cell Growth Differ. (United States) 12 (4): 193–200. ISSN 1044-9523. PMID 11331248.
- ^ Melander, Fredrik; Andersson Tommy, Dib Karim (March 2003). "Fgr but not Syk tyrosine kinase is a target for beta 2 integrin-induced c-Cbl-mediated ubiquitination in adherent human neutrophils". Biochem. J. (England) 370 (Pt 2): 687–94. DOI:10.1042/BJ20021201. ISSN 0264-6021. PMC 1223185. PMID 12435267. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223185.
- ^ Yokouchi, M; Kondo T, Houghton A, Bartkiewicz M, Horne W C, Zhang H, Yoshimura A, Baron R (October 1999). "Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7". J. Biol. Chem. (UNITED STATES) 274 (44): 31707–12. DOI:10.1074/jbc.274.44.31707. ISSN 0021-9258. PMID 10531381.
- ^ Zheng, N; Wang P, Jeffrey P D, Pavletich N P (August 2000). "Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases". Cell (UNITED STATES) 102 (4): 533–9. DOI:10.1016/S0092-8674(00)00057-X. ISSN 0092-8674. PMID 10966114.
- ^ Marengère, L E; Mirtsos C, Kozieradzki I, Veillette A, Mak T W, Penninger J M (July 1997). "Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells". J. Immunol. (UNITED STATES) 159 (1): 70–6. ISSN 0022-1767. PMID 9200440.
- ^ Pedraza-Alva, G; Sawasdikosol S, Liu Y C, Mérida L B, Cruz-Muñoz M E, Oceguera-Yañez F, Burakoff S J, Rosenstein Y (January 2001). "Regulation of Cbl molecular interactions by the co-receptor molecule CD43 in human T cells". J. Biol. Chem. (UNITED STATES) 276 (1): 729–37. DOI:10.1074/jbc.M008494200. ISSN 0021-9258. PMID 11024037.
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- ^ Lupher, M L; Reedquist K A, Miyake S, Langdon W Y, Band H (September 1996). "A novel phosphotyrosine-binding domain in the N-terminal transforming region of Cbl interacts directly and selectively with ZAP-70 in T cells". J. Biol. Chem. (UNITED STATES) 271 (39): 24063–8. DOI:10.1074/jbc.271.39.24063. ISSN 0021-9258. PMID 8798643.
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PDB gallery
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1b47: STRUCTURE OF THE N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE IN ZAP-70
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1fbv: STRUCTURE OF A CBL-UBCH7 COMPLEX: RING DOMAIN FUNCTION IN UBIQUITIN-PROTEIN LIGASES
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1yvh: Crystal Structure of the c-Cbl TKB Domain in Complex with the APS pTyr-618 Phosphopeptide
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2cbl: N-TERMINAL DOMAIN OF CBL IN COMPLEX WITH ITS BINDING SITE ON ZAP-70
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2oo9: crystal structure of the UBA domain from human c-Cbl ubiquitin ligase
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Chaperones/
protein folding |
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Hsp10/GroES (Early pregnancy factor) · Hsp27 · Hsp47 · HSP60/GroEL
Hsp40/DnaJ (A1, A2, A3, B1, B2, B11, B4, B6, B9, C1, C3, C5, C6, C7, C10, C11, C13, C14, C19)
Hsp70 (1A, 1B, 1L, 2, 4, 4L, 5, 6, 7, 8, 9, 12A, 14)
Hsp90 ( α1, α2, β, ER, TRAP1)
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Other
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Protein targeting |
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Ubiquitin |
E1 Ubiquitin-activating enzyme (UBA1, UBA2, UBA3, UBA5, UBA6, UBA7, ATG7, NAE1, SAE1)
E2 Ubiquitin-conjugating enzyme (A • B • C • D1, D2, D3 • E1, E2, E3 • G1, G2 • H • I • J1, J2 • K • L1, L2, L3, L4, L6 • M • N • O • Q1, Q2 • R1 (CDC34), R2 • S • V1, V2 • Z)
E3 Ubiquitin ligase (VHL, Cullin, CBL, MDM2, FANCL, UBR1)
Deubiquitinating enzyme: Ataxin 3 • USP6 • CYLD
ATG3 • BIRC6 • UFC1
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Other |
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see also posttranslational modification disorders
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
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