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CBL
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, 4GPL
Identifiers
Aliases	CBL, C-CBL2, FRA11B, NSLL, RNF55, Cbl proto-oncogene
External IDs	OMIM: 165360; MGI: 88279; HomoloGene: 3802; GeneCards: CBL; OMA:CBL - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q23.3 Start 119,206,298 bp End 119,313,926 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 A5.1- A5.2|9 24.72 cM Start 44,054,273 bp End 44,145,346 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad trigeminal ganglion testicle trabecular bone saphenous vein spinal ganglia superficial temporal artery nipple blood visceral pleura Top expressed in thymus granulocyte Rostral migratory stream spermatocyte tail of embryo spermatid mesenteric lymph nodes lateral septal nucleus anterior amygdaloid area blood More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding DNA-binding transcription factor activity phosphotyrosine residue binding signal transducer activity metal ion binding ubiquitin-protein transferase activity protein binding ephrin receptor binding SH3 domain binding phosphatidylinositol 3-kinase regulatory subunit binding transferase activity receptor tyrosine kinase binding ubiquitin protein ligase activity cadherin binding epidermal growth factor receptor binding protein kinase binding protein tyrosine kinase binding Cellular component membrane plasma membrane nucleus perinuclear region of cytoplasm flotillin complex growth cone cytoplasm cytosol focal adhesion axon mast cell granule membrane raft Golgi apparatus cilium cell projection Biological process positive regulation of receptor-mediated endocytosis negative regulation of epidermal growth factor receptor signaling pathway epidermal growth factor receptor signaling pathway negative regulation of apoptotic process regulation of signaling fibroblast growth factor receptor signaling pathway cell surface receptor signaling pathway protein ubiquitination positive regulation of phosphatidylinositol 3-kinase signaling transforming growth factor beta receptor signaling pathway cellular response to DNA damage stimulus cellular response to nerve growth factor stimulus cellular response to platelet-derived growth factor stimulus positive regulation of epidermal growth factor receptor signaling pathway regulation of transcription, DNA-templated neuron death cellular response to oxygen-glucose deprivation response to activity response to starvation response to ethanol protein polyubiquitination protein monoubiquitination negative regulation of epidermal growth factor-activated receptor activity male gonad development response to gamma radiation response to testosterone entry of bacterium into host cell mast cell degranulation response to antibiotic membrane organization negative regulation of neuron death cytokine-mediated signaling pathway interleukin-6-mediated signaling pathway ubiquitin-dependent protein catabolic process signal transduction regulation of Rap protein signal transduction cellular response to epidermal growth factor stimulus regulation of platelet-derived growth factor receptor-alpha signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 867 12402 Ensembl ENSG00000110395 ENSMUSG00000034342 UniProt P22681 P22682 RefSeq (mRNA) NM_005188 NM_007619 RefSeq (protein) NP_005179 NP_031645 Location (UCSC) Chr 11: 119.21 – 119.31 Mb Chr 9: 44.05 – 44.15 Mb PubMed search
Wikidata
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Cbl (named after Casitas B-lineage Lymphoma) is a mammalian gene family. CBL gene, a part of the Cbl family, encodes the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.

Discovery

In 1989 a virally encoded portion of the chromosomal mouse Cbl gene was the first member of the Cbl family to be discovered and was named v-Cbl to distinguish it from normal mouse c-Cbl. The virus used in the experiment was a mouse-tropic strain of Murine leukemia virus isolated from the brain of a mouse captured at Lake Casitas, California known as Cas-Br-M, and was found to have excised approximately a third of the original c-Cbl gene from a mouse into which it was injected. 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 tumor 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.

Structure

Full length c-Cbl has been found to consist of several regions encoding for functionally distinct protein domains:

• N-terminal tyrosine kinase binding domain (TKB domain): determines the protein which it can bind to
• RING finger domain motif: recruits enzymes involved in ubiquitination
• Proline-rich region: the site of interaction between Cbl and cytosolic proteins involved in Cbl's adaptor functions
• C-terminal ubiquitin-associated domain (UBA domain): the site of ubiquitin binding

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.

Homologues

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:

1. c-Cbl: ubiquitously expressed, 906 and 913 amino acids in length in humans and mice respectively
2. Cbl-b: ubiquitously expressed, 982 amino acids long.
3. 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.

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.

Function

Ubiquitin ligase

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.

Interactions

Cbl gene has been shown to interact with:

• Abl gene,
• ARHGEF7,
• C-Met,
• CD2AP,
• CSF1R.
• CRK,
• CRKL,
• EGFR,<
• FRS2,
• FYN,
• Grb2,
• HCK,
• IGF1R,
• LCP2,
• NCK1,
• PDGFRA,
• PIK3R1,
• PIK3R2,
• PLCG1,
• PTK2B,
• PTPN11,
• SH2B2,
• SH3KBP1
• SHC1,
• SLA2,
• SORBS1,
• SORBS2,
• SPRY2,
• Syk,
• UBE2L3,
• VAV1,
• YWHAB,
• YWHAQ, and
• ZAP-70,

References

1. ^ GRCh38: Ensembl release 89: ENSG00000110395 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000034342 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Naramura M, Nadeau S, Mohapatra B, Ahmad G, Mukhopadhyay C, Sattler M, Raja SM, Natarajan A, Band V, Band H (2011). "Mutant Cbl proteins as oncogenic drivers in myeloproliferative disorders". Oncotarget. 2 (3): 245–50. doi:10.18632/oncotarget.233. PMC 3134300. PMID 21422499.
6. 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. Bibcode:1989PNAS...86.1168L. doi:10.1073/pnas.86.4.1168. PMC 286647. PMID 2784003.
7. Hartley JW, Rowe WP (July 1976). "Naturally occurring murine leukemia viruses in wild mice: characterization of a new "amphotropic" class". Journal of Virology. 19 (1): 21. doi:10.1128/JVI.19.1.19-25.1976. PMC 354828. PMID 59816.
8. ^ 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. S2CID 1527924.
9. ^ Miyoshi-Akiyama T, Aleman LM, Smith JM, Adler CE, Mayer BJ (July 2001). "Regulation of Cbl phosphorylation by the Abl tyrosine kinase and the Nck SH2/SH3 adaptor". Oncogene. 20 (30): 4058–69. doi:10.1038/sj.onc.1204528. PMID 11494134.
10. ^ 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.
11. 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. Bibcode:2003FEBSL.550..119F. doi:10.1016/S0014-5793(03)00853-6. PMID 12935897. S2CID 46540220.
12. ^ Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J (March 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. 27 (5): 804–16. doi:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061.
13. ^ 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. Bibcode:2002Natur.416..187P. doi:10.1038/416187a. PMID 11894096. S2CID 4389099.
14. ^ Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I (May 2004). "Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites". J. Cell Sci. 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. PMID 15128873. S2CID 14083271.
15. 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.
16. Cormont M, Metón I, Mari M, Monzo P, Keslair F, Gaskin C, McGraw TE, Le Marchand-Brustel Y (February 2003). "CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl". Traffic. 4 (2): 97–112. doi:10.1034/j.1600-0854.2003.40205.x. PMID 12559036. S2CID 38612642.
17. 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.
18. ^ 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. 273 (7): 3986–93. doi:10.1074/jbc.273.7.3986. PMID 9461587.
19. ^ 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. S2CID 967748.
20. ^ Erdreich-Epstein A, Liu M, Kant AM, Izadi KD, Nolta JA, Durden DL (April 1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. 65 (4): 523–34. doi:10.1002/jlb.65.4.523. PMID 10204582. S2CID 18340540.
21. ^ 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.
22. 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. doi:10.4049/jimmunol.161.10.5555. PMID 9820532. S2CID 255369788.
23. 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. doi:10.4049/jimmunol.160.10.5018. PMID 9590251. S2CID 9556579.
24. ^ 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. doi:10.4049/jimmunol.169.7.3793. PMID 12244174.
25. 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.
26. 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. hdl:20.500.12613/9173. PMID 9162067.
27. 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.
28. ^ 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.
29. 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.
30. ^ Wong A, Lamothe B, Lee A, Schlessinger J, Lax I, Li A (May 2002). "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proc. Natl. Acad. Sci. U.S.A. 99 (10): 6684–9. Bibcode:2002PNAS...99.6684W. doi:10.1073/pnas.052138899. PMC 124463. PMID 11997436.
31. 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.
32. ^ Park RK, Erdreich-Epstein A, Liu M, Izadi KD, Durden DL (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. 163 (11): 6023–34. doi:10.4049/jimmunol.163.11.6023. PMID 10570290. S2CID 36719981.
33. Jain SK, Langdon WY, Varticovski L (May 1997). "Tyrosine phosphorylation of p120cbl in BCR/abl transformed hematopoietic cells mediates enhanced association with phosphatidylinositol 3-kinase". Oncogene. 14 (18): 2217–28. doi:10.1038/sj.onc.1201049. PMID 9174058.
34. Liu SK, McGlade CJ (December 1998). "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc". Oncogene. 17 (24): 3073–82. doi:10.1038/sj.onc.1202337. PMID 9872323. S2CID 6140122.
35. Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S (March 1999). "cbl-b inhibits epidermal growth factor receptor signaling". Oncogene. 18 (10): 1855–66. doi:10.1038/sj.onc.1202499. PMID 10086340.
36. ^ Robertson H, Langdon WY, Thien CB, Bowtell DD (November 1997). "A c-Cbl yeast two hybrid screen reveals interactions with 14-3-3 isoforms and cytoskeletal components". Biochem. Biophys. Res. Commun. 240 (1): 46–50. doi:10.1006/bbrc.1997.7608. PMID 9367879.
37. Donovan JA, Wange RL, Langdon WY, Samelson LE (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. 269 (37): 22921–4. doi:10.1016/S0021-9258(17)31595-8. PMID 8083187.
38. Saci A, Liu WQ, Vidal M, Garbay C, Rendu F, Bachelot-Loza C (May 2002). "Differential effect of the inhibition of Grb2-SH3 interactions in platelet activation induced by thrombin and by Fc receptor engagement". Biochem. J. 363 (Pt 3): 717–25. doi:10.1042/0264-6021:3630717. PMC 1222524. PMID 11964172.
39. 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. 89 (8): 2745–56. doi:10.1182/blood.V89.8.2745. PMID 9108392.
40. Howlett CJ, Robbins SM (March 2002). "Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated cellular transformation". Oncogene. 21 (11): 1707–16. doi:10.1038/sj.onc.1205228. PMID 11896602. S2CID 34296309.
41. Howlett CJ, Bisson SA, Resek ME, Tigley AW, Robbins SM (April 1999). "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase". Biochem. Biophys. Res. Commun. 257 (1): 129–38. doi:10.1006/bbrc.1999.0427. PMID 10092522.
42. Sehat B, Andersson S, Girnita L, Larsson O (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. 68 (14): 5669–77. doi:10.1158/0008-5472.CAN-07-6364. PMID 18632619.
43. Park RK, Izadi KD, Deo YM, Durden DL (September 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling". Blood. 94 (6): 2112–20. doi:10.1182/blood.V94.6.2112. PMID 10477741.
44. Bonita DP, Miyake S, Lupher ML, Langdon WY, 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. 17 (8): 4597–610. doi:10.1128/mcb.17.8.4597. PMC 232313. PMID 9234717.
45. Zhang S, Broxmeyer HE (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. 254 (2): 440–5. doi:10.1006/bbrc.1998.9959. PMID 9918857.
46. Dufour C, Guenou H, Kaabeche K, Bouvard D, Sanjay A, Marie PJ (June 2008). "FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival". Bone. 42 (6): 1032–9. doi:10.1016/j.bone.2008.02.009. PMID 18374639.
47. 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. 270 (31): 18260–3. doi:10.1074/jbc.270.31.18260. PMID 7629144.
48. Graham LJ, Stoica BA, Shapiro M, DeBell KE, 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. 249 (2): 537–41. doi:10.1006/bbrc.1998.9177. PMID 9712732.
49. Sanjay A, Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne WC, 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. 152 (1): 181–95. doi:10.1083/jcb.152.1.181. PMC 2193648. PMID 11149930.
50. Tanaka Y, Tanaka N, Saeki Y, Tanaka K, Murakami M, Hirano T, Ishii N, Sugamura K (August 2008). "c-Cbl-dependent monoubiquitination and lysosomal degradation of gp130". Mol. Cell. Biol. 28 (15): 4805–18. doi:10.1128/MCB.01784-07. PMC 2493370. PMID 18519587.
51. 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. 13 (5): 760–7. doi:10.1038/sj/leu/2401397. PMID 10374881.
52. Watanabe S, Take H, Takeda K, Yu ZX, Iwata N, Kajigaya S (November 2000). "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochem. Biophys. Res. Commun. 278 (1): 167–74. doi:10.1006/bbrc.2000.3760. PMID 11071869.
53. Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I (March 2002). "Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors". Nature. 416 (6877): 183–7. Bibcode:2002Natur.416..183S. doi:10.1038/416183a. PMID 11894095. S2CID 635702.
54. Szymkiewicz I, Kowanetz K, Soubeyran P, Dinarina A, Lipkowitz S, Dikic I (October 2002). "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases". J. Biol. Chem. 277 (42): 39666–72. doi:10.1074/jbc.M205535200. PMID 12177062.
55. Borinstein SC, Hyatt MA, Sykes VW, Straub RE, 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. 12 (11–12): 769–79. doi:10.1016/S0898-6568(00)00129-7. PMID 11152963.
56. Pandey A, Ibarrola N, Kratchmarova I, Fernandez MM, Constantinescu SN, Ohara O, Sawasdikosol S, Lodish HF, Mann M (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. 277 (21): 19131–8. doi:10.1074/jbc.M110318200. PMID 11891219.
57. Vandenbroere I, Paternotte N, Dumont JE, Erneux C, Pirson I (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. 300 (2): 494–500. doi:10.1016/S0006-291X(02)02894-2. PMID 12504111.
58. ^ Wong ES, Fong CW, Lim J, Yusoff P, Low BC, Langdon WY, Guy GR (September 2002). "Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling". EMBO J. 21 (18): 4796–808. doi:10.1093/emboj/cdf493. PMC 126289. PMID 12234920.
59. Wong ES, Lim J, Low BC, Chen Q, Guy GR (February 2001). "Evidence for direct interaction between Sprouty and Cbl". J. Biol. Chem. 276 (8): 5866–75. doi:10.1074/jbc.M006945200. PMID 11053437.
60. Lupher ML, Rao N, Lill NL, Andoniou CE, Miyake S, Clark EA, 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. 273 (52): 35273–81. doi:10.1074/jbc.273.52.35273. PMID 9857068.
61. ^ Bertagnolo V, Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi ML, Capitani S (April 2001). "Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells". Cell Growth Differ. 12 (4): 193–200. PMID 11331248.
62. Melander F, Andersson T, Dib K (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. 370 (Pt 2): 687–94. doi:10.1042/BJ20021201. PMC 1223185. PMID 12435267.
63. Yokouchi M, Kondo T, Houghton A, Bartkiewicz M, Horne WC, 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. 274 (44): 31707–12. doi:10.1074/jbc.274.44.31707. PMID 10531381.
64. Zheng N, Wang P, Jeffrey PD, Pavletich NP (August 2000). "Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases". Cell. 102 (4): 533–9. doi:10.1016/S0092-8674(00)00057-X. PMID 10966114. S2CID 14132429.
65. Marengère LE, Mirtsos C, Kozieradzki I, Veillette A, Mak TW, Penninger JM (July 1997). "Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells". J. Immunol. 159 (1): 70–6. doi:10.4049/jimmunol.159.1.70. PMID 9200440. S2CID 33688953.
66. Pedraza-Alva G, Sawasdikosol S, Liu YC, Mérida LB, Cruz-Muñoz ME, Oceguera-Yañez F, Burakoff SJ, Rosenstein Y (January 2001). "Regulation of Cbl molecular interactions by the co-receptor molecule CD43 in human T cells". J. Biol. Chem. 276 (1): 729–37. doi:10.1074/jbc.M008494200. PMID 11024037.
67. Liu YC, Elly C, Yoshida H, Bonnefoy-Berard N, Altman A (June 1996). "Activation-modulated association of 14-3-3 proteins with Cbl in T cells". J. Biol. Chem. 271 (24): 14591–5. doi:10.1074/jbc.271.24.14591. PMID 8663231.
68. Lupher ML, Reedquist KA, Miyake S, Langdon WY, 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. 271 (39): 24063–8. doi:10.1074/jbc.271.39.24063. PMID 8798643.
69. Meng W, Sawasdikosol S, Burakoff SJ, Eck MJ (March 1999). "Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase". Nature. 398 (6722): 84–90. Bibcode:1999Natur.398...84M. doi:10.1038/18050. PMID 10078535. S2CID 4411124.

Further reading

• Smit L, Borst J (1997). "The Cbl family of signal transduction molecules". Crit Rev Oncog. 8 (4): 359–79. doi:10.1615/critrevoncog.v8.i4.50. PMID 9622055.
• Lupher ML, Andoniou CE, Bonita D, Miyake S, Band H (1998). "The c-Cbl oncoprotein". Int. J. Biochem. Cell Biol. 30 (4): 439–44. doi:10.1016/S1357-2725(97)00075-7. PMID 9675877.
• Fang N, Fang D, Wang HY, Altman A, Liu YC (2002). "Regulation of immune responses by E3 ubiquitin-protein ligases". Curr. Dir. Autoimmun. Current Directions in Autoimmunity. 5: 161–75. doi:10.1159/000060552. ISBN 3-8055-7308-1. PMID 11826757.

External links

• Quips article describing CBL function at PDBe
• OMIM entries on NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MYELOMONOCYTIC LEUKEMIA and CBL
• Human CBL genome location and CBL gene details page in the UCSC Genome Browser.

• Genes on human chromosome 11
• Proteins