CBL linker region and RING finger mutations lead to enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling via elevated levels of JAK2 and LYN

Journal of Biological Chemistry

Volumn 288, Issue 27, 2013, Pages 19459-19470

  Javadi, Mojib ^a,b   Richmond, Terri D ^a,b   Huang, Kai ^b   Barber, Dwayne L ^a,b  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ELEVATED LEVEL; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTORS; KINASE ACTIVITY; LINKER REGION; MUTANT CELLS; RING FINGER; SMALL MOLECULE INHIBITOR; TF-1 CELLS;

CELL CULTURE; ENZYMES; PHOSPHORYLATION; SIGNALING;

MACROPHAGES;

DASATINIB; FEDRATINIB; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; JANUS KINASE 2; MUTANT PROTEIN; PROTEIN C384R; PROTEIN CBL Y371H; PROTEIN KINASE LYN; RING FINGER PROTEIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

ARTICLE; CELL MUTANT; CELL SURVIVAL; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; JUVENILE MYELOMONOCYTIC LEUKEMIA; MUTATION; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION;

CBL; CYTOKINE; E3 UBIQUITIN LIGASE; GM-CSF; JAK KINASE; JUVENILE MYELOMONOCYTIC LEUKEMIA; SIGNAL TRANSDUCTION; SRC;

AMINO ACID SUBSTITUTION; CELL LINE; CYTOKINE RECEPTOR COMMON BETA SUBUNIT; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, LEUKEMIC; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; HUMANS; JANUS KINASE 2; LEUKEMIA, MYELOMONOCYTIC, JUVENILE; MUTATION, MISSENSE; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-CBL; PYRIMIDINES; PYRROLIDINES; RING FINGER DOMAINS; SIGNAL TRANSDUCTION; SRC-FAMILY KINASES; SULFONAMIDES; THIAZOLES;

EID: 84880062396     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.475087     Document Type: Article

References (82)

1. Hercus, T. R., Broughton, S. E., Ekert, P. G., Ramshaw, H. S., Perugini, M., Grimbaldeston, M., Woodcock, J. M., Thomas, D., Pitson, S., Hughes, T., D'Andrea, R. J., Parker, M. W., and Lopez, A. F. (2012) The GM-CSF receptor family. Mechanism of activation and implications for disease. Growth Factors 30, 63-75
2. Park, L. S., Martin, U., Sorensen, R., Luhr, S., Morrissey, P. J., Cosman, D., and Larsen, A. (1992) Cloning of the low-affinity murine granulocytemacrophage colony-stimulating factor receptor and reconstitution of a high-affinity receptor complex. Proc. Natl. Acad. Sci. U.S.A. 89, 4295-4299
3. Hayashida, K., Kitamura, T., Gorman, D. M., Arai, K., Yokota, T., and Miyajima, A. (1990) Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GMCSF). Reconstitution of a high-affinity GM-CSF receptor. Proc. Natl. Acad. Sci. U.S.A. 87, 9655-9659
4. Barreda, D. R., Hanington, P. C., and Belosevic, M. (2004) Regulation of myeloid development and function by colony stimulating factors. Dev. Comp. Immunol. 28, 509-554
5. Gearing, D. P., King, J. A., Gough, N. M., and Nicola, N. A. (1989) Expres-sion cloning of a receptor for human granulocyte-macrophage colonystimulating factor. EMBO J. 8, 3667-3676
6. Hansen, G., Hercus, T. R., McClure, B. J., Stomski, F. C., Dottore, M., Powell, J., Ramshaw, H., Woodcock, J. M., Xu, Y., Guthridge, M., Mc-Kinstry, W. J., Lopez, A. F., and Parker, M. W. (2008) The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 134, 496-507
7. Emanuel, P. D. (2008) Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Leukemia 22, 1335-1342
8. Chan, R. J., Cooper, T., Kratz, C. P., Weiss, B., and Loh, M. L. (2009) Juvenile myelomonocytic leukemia. A report from the 2nd International JMML Symposium. Leuk. Res. 33, 355-362
9. Side, L. E., Emanuel, P. D., Taylor, B., Franklin, J., Thompson, P., Castleberry, R. P., and Shannon, K. M. (1998) Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1. Blood 92, 267-272
10. Side, L., Taylor, B., Cayouette, M., Conner, E., Thompson, P., Luce, M., and Shannon, K. (1997) Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. N. Engl. J. Med. 336, 1713-1720
11. Xu, G. F., Lin, B., Tanaka, K., Dunn, D., Wood, D., Gesteland, R., White, R., Weiss, R., and Tamanoi, F. (1990) The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell 63, 835-841
12. Tartaglia, M., Niemeyer, C. M., Fragale, A., Song, X., Buechner, J., Jung, A., Hählen, K., Hasle, H., Licht, J. D., and Gelb, B. D. (2003) Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat. Genet. 34, 148-150
13. Loh, M. L., Vattikuti, S., Schubbert, S., Reynolds, M. G., Carlson, E., Lieuw, K. H., Cheng, J. W., Lee, C. M., Stokoe, D., Bonifas, J. M., Curtiss, N. P., Gotlib, J., Meshinchi, S., Le Beau, M. M., Emanuel, P. D., and Shannon, K. M. (2004) Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Blood 103, 2325-2331
14. Kratz, C. P., Niemeyer, C. M., Castleberry, R. P., Cetin, M., Bergsträsser, E., Emanuel, P. D., Hasle, H., Kardos, G., Klein, C., Kojima, S., Stary, J., Trebo, M., Zecca, M., Gelb, B. D., Tartaglia, M., and Loh, M. L. (2005) The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. Blood 106, 2183-2185
15. Noguchi, T., Matozaki, T., Horita, K., Fujioka, Y., and Kasuga, M. (1994) Role of SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in insulin-stimulated Ras activation. Mol. Cell Biol. 14, 6674-6682
16. Shi, Z. Q., Yu, D. H., Park, M., Marshall, M., and Feng, G. S. (2000) Molecular mechanism for the Shp-2 tyrosine phosphatase function in promoting growth factor stimulation of Erk activity. Mol. Cell Biol. 20, 1526-1536
17. Kalra, R., Paderanga, D. C., Olson, K., and Shannon, K. M. (1994) Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras. Blood 84, 3435-3439
18. Miyauchi, J., Asada, M., Sasaki, M., Tsunematsu, Y., Kojima, S., and Mizutani, S. (1994) Mutations of the N-ras gene in juvenile chronic myelogenous leukemia. Blood 83, 2248-2254
19. Flotho, C., Valcamonica, S., Mach-Pascual, S., Schmahl, G., Corral, L., Ritterbach, J., Hasle, H., Arico, M., Biondi, A., and Niemeyer, C. M. (1999) RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 13, 32-37
20. Muramatsu, H., Makishima, H., Jankowska, A. M., Cazzolli, H., O'Keefe, C., Yoshida, N., Xu, Y., Nishio, N., Hama, A., Yagasaki, H., Takahashi, Y., Kato, K., Manabe, A., Kojima, S., and Maciejewski, J. P. (2010) Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia. Blood 115, 1969-1975
21. Loh, M. L., Sakai, D. S., Flotho, C., Kang, M., Fliegauf, M., Archambeault, S., Mullighan, C. G., Chen, L., Bergstraesser, E., Bueso-Ramos, C. E., Emanuel, P. D., Hasle, H., Issa, J. P., van den Heuvel-Eibrink, M. M., Locatelli, F., Stary, J., Trebo, M., Wlodarski, M., Zecca, M., Shannon, K. M., and Niemeyer, C. M. (2009) Mutations in CBL occur frequently in juvenile myelomonocytic leukemia. Blood 114, 1859-1863
22. Makishima, H., Cazzolli, H., Szpurka, H., Dunbar, A., Tiu, R., Huh, J., Muramatsu, H., O'Keefe, C., Hsi, E., Paquette, R. L., Kojima, S., List, A. F., Sekeres, M. A., McDevitt, M. A., and Maciejewski, J. P. (2009) Mutations of e3 ubiquitin ligase cbl family members constitute a novel common pathogenic lesion in myeloid malignancies. J. Clin. Oncol. 27, 6109-6116
23. Sanada, M., Suzuki, T., Shih, L. Y., Otsu, M., Kato, M., Yamazaki, S., Tamura, A., Honda, H., Sakata-Yanagimoto, M., Kumano, K., Oda, H., Yamagata, T., Takita, J., Gotoh, N., Nakazaki, K., Kawamata, N., Onodera, M., Nobuyoshi, M., Hayashi, Y., Harada, H., Kurokawa, M., Chiba, S., Mori, H., Ozawa, K., Omine, M., Hirai, H., Nakauchi, H., Koeffler, H. P., and Ogawa, S. (2009) Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. Nature 460, 904-908
24. Fernandes, M. S., Reddy, M. M., Croteau, N. J., Walz, C., Weisbach, H., Podar, K., Band, H., Carroll, M., Reiter, A., Larson, R. A., Salgia, R., Griffin, J. D., and Sattler, M. (2010) Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism. J. Biol. Chem. 285, 32596-32605
25. Sargin, B., Choudhary, C., Crosetto, N., Schmidt, M. H., Grundler, R., Rensinghoff, M., Thiessen, C., Tickenbrock, L., Schwäble, J., Brandts, C., August, B., Koschmieder, S., Bandi, S. R., Duyster, J., Berdel, W. E.,Müller-Tidow, C., Dikic, I., and Serve, H. (2007) Flt3-dependent transformation by inactivating c-Cbl mutations in AML. Blood 110, 1004-1012
26. Dunbar, A. J., Gondek, L. P., O'Keefe, C. L., Makishima, H., Rataul, M. S., Szpurka, H., Sekeres, M. A., Wang, X. F., McDevitt, M. A., and Maciejewski, J. P. (2008) 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res. 68, 10349-10357
27. Grand, F. H., Hidalgo-Curtis, C. E., Ernst, T., Zoi, K., Zoi, C., McGuire, C., Kreil, S., Jones, A., Score, J., Metzgeroth, G., Oscier, D., Hall, A., Brandts, C., Serve, H., Reiter, A., Chase, A. J., and Cross, N. C. (2009) Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 113, 6182-6192
28. Reindl, C., Quentmeier, H., Petropoulos, K., Greif, P. A., Benthaus, T., Argiropoulos, B., Mellert, G., Vempati, S., Duyster, J., Buske, C., Bohlander, S. K., Humphries, K. R., Hiddemann, W., and Spiekermann, K. (2009) CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes. Clin. Cancer Res. 15, 2238-2247
29. Levkowitz, G., Waterman, H., Ettenberg, S. A., Katz, M., Tsygankov, A. Y., Alroy, I., Lavi, S., Iwai, K., Reiss, Y., Ciechanover, A., Lipkowitz, S., and Yarden, Y. (1999) Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol. Cell 4, 1029-1040
30. Dou, H., Buetow, L., Hock, A., Sibbet, G. J., Vousden, K. H., and Huang, D. T. (2012) Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl. Nat. Struct. Mol. Biol. 19, 184-192
31. Kassenbrock, C. K., and Anderson, S. M. (2004) Regulation of ubiquitin protein ligase activity in c-Cbl by phosphorylation-induced conformational change and constitutive activation by tyrosine to glutamate point mutations. J. Biol. Chem. 279, 28017-28027
32. Joazeiro, C. A., Wing, S. S., Huang, H., Leverson, J. D., Hunter, T., and Liu, Y. C. (1999) The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science 286, 309-312
33. Anderson, S. M., Burton, E. A., and Koch, B. L. (1997) Phosphorylation of Cbl following stimulation with interleukin-3 and its association with Grb2, Fyn, and phosphatidylinositol 3-kinase. J. Biol. Chem. 272, 739-745
34. Barber, D. L., Mason, J. M., Fukazawa, T., Reedquist, K. A., Druker, B. J., Band, H., and D'Andrea, A. D. (1997) Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins. Blood 89, 3166-3174
35. Naccache, P. H., Gilbert, C., Barabé, F., Al-Shami, A., Mahana, W., and Bourgoin, S. G. (1997) Agonist-specific tyrosine phosphorylation of Cbl in human neutrophils. J. Leukoc. Biol. 62, 901-910
36. Odai, H., Sasaki, K., Iwamatsu, A., Hanazono, Y., Tanaka, T., Mitani, K., Yazaki, Y., and Hirai, H. (1995) The proto-oncogene product c-Cbl becomes tyrosine phosphorylated by stimulation with GM-CSF or Epo and constitutively binds to the SH3 domain of Grb2/Ash in human hematopoietic cells. J. Biol. Chem. 270, 10800-10805
37. Martinez-Moczygemba, M., and Huston, D. P. (2001) Proteasomal regulation of βc signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization. J. Clin. Invest. 108, 1797-1806
38. Kitamura, T., Tange, T., Terasawa, T., Chiba, S., Kuwaki, T., Miyagawa, K., Piao, Y. F., Miyazono, K., Urabe, A., and Takaku, F. (1989) Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. J. Cell Physiol. 140, 323-334
39. Emanuel, P. D., Bates, L. J., Castleberry, R. P., Gualtieri, R. J., and Zuckerman, K. S. (1991) Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood 77, 925-929
40. Niemeyer, C. M., Kang, M. W., Shin, D. H., Furlan, I., Erlacher, M., Bunin, N. J., Bunda, S., Finklestein, J. Z., Sakamoto, K. M., Gorr, T. A., Mehta, P., Schmid, I., Kropshofer, G., Corbacioglu, S., Lang, P. J., Klein, C., Schlegel, P. G., Heinzmann, A., Schneider, M., Starý, J., van den Heuvel-Eibrink, M. M., Hasle, H., Locatelli, F., Sakai, D., Archambeault, S., Chen, L., Russell, R. C., Sybingco, S. S., Ohh, M., Braun, B. S., Flotho, C., and Loh, M. L. (2010) Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat. Genet. 42, 794-800
41. Saur, S. J., Sangkhae, V., Geddis, A. E., Kaushansky, K., and Hitchcock, I. S. (2010) Ubiquitination and degradation of the thrombopoietin receptor c-Mpl. Blood 115, 1254-1263
42. Tanaka, Y., Tanaka, N., Saeki, Y., Tanaka, K., Murakami, M., Hirano, T., Ishii, N., and Sugamura, K. (2008) c-Cbl-dependent monoubiquitination and lysosomal degradation of gp130. Mol. Cell Biol. 28, 4805-4818
43. Thien, C. B., Walker, F., and Langdon, W. Y. (2001) RING finger mutations that abolish c-Cbl-directed polyubiquitination and downregulation of the EGF receptor are insufficient for cell transformation. Mol. Cell 7, 355-365
44. Quelle, F. W., Sato, N., Witthuhn, B. A., Inhorn, R. C., Eder, M., Miyajima, A., Griffin, J. D., and Ihle, J. N. (1994) JAK2 associates with the β c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. Mol. Cell Biol. 14, 4335-4341
45. Brizzi, M. F., Zini, M. G., Aronica, M. G., Blechman, J. M., Yarden, Y., and Pegoraro, L. (1994) Convergence of signaling by interleukin-3, granulocyte-macrophage colony-stimulating factor, and mast cell growth factor on JAK2 tyrosine kinase. J. Biol. Chem. 269, 31680-31684
46. Parganas, E., Wang, D., Stravopodis, D., Topham, D. J., Marine, J. C., Teglund, S., Vanin, E. F., Bodner, S., Colamonici, O. R., van Deursen, J. M., Grosveld, G., and Ihle, J. N. (1998) Jak2 is essential for signaling through a variety of cytokine receptors. Cell 93, 385-395
47. Watanabe, S., Itoh, T., and Arai, K. (1996) Roles of JAK kinases in human GM-CSF receptor signal transduction. J. Allergy Clin. Immunol. 98, S183-S191
48. Perugini, M., Brown, A. L., Salerno, D. G., Booker, G. W., Stojkoski, C., Hercus, T. R., Lopez, A. F., Hibbs, M. L., Gonda, T. J., and D'Andrea, R. J. (2010) Alternative modes of GM-CSF receptor activation revealed using activated mutants of the common β-subunit. Blood 115, 3346-3353
49. Wei, S., Liu, J. H., Epling-Burnette, P. K., Gamero, A. M., Ussery, D., Pearson, E. W., Elkabani, M. E., Diaz, J. I., and Djeu, J. Y. (1996) Critical role of Lyn kinase in inhibition of neutrophil apoptosis by granulocyte- macrophage colony-stimulating factor. J. Immunol. 157, 5155-5162
50. Corey, S., Eguinoa, A., Puyana-Theall, K., Bolen, J. B., Cantley, L., Mollinedo, F., Jackson, T. R., Hawkins, P. T., and Stephens, L. R. (1993) Granulocyte macrophage-colony stimulating factor stimulates both association and activation of phosphoinositide 3OH-kinase and src-related tyrosine kinase(s) in human myeloid derived cells.EMBOJ. 12, 2681-2690
51. Li, Y., Shen, B. F., Karanes, C., Sensenbrenner, L., and Chen, B. (1995) Association between Lyn protein tyrosine kinase (p53/56lyn) and the β subunit of the granulocyte-macrophage colony-stimulating factor (GMCSF) receptors in a GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e). J. Immunol. 155, 2165-2174
52. Yousefi, S., Hoessli, D. C., Blaser, K., Mills, G. B., and Simon, H. U. (1996) Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils. J. Exp. Med. 183, 1407-1414
53. Tsygankov, A. Y., Teckchandani, A. M., Feshchenko, E. A., and Swaminathan, G. (2001) Beyond the RING. CBL proteins as multivalent adapters. Oncogene 20, 6382-6402
54. Feshchenko, E. A., Langdon, W. Y., and Tsygankov, A. Y. (1998) Fyn, Yes, and Syk phosphorylation sites in c-Cbl map to the same tyrosine residues that become phosphorylated in activated T cells. J. Biol. Chem. 273, 8323-8331
55. Marengere, L. E., Mirtsos, C., Kozieradzki, I., Veillette, A., Mak, T. W., and Penninger, J. M. (1997) Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells. J. Immunol. 159, 70-76
56. Liu, Y. C., Elly, C., Langdon, W. Y., and Altman, A. (1997) Ras-dependent, Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells. J. Biol. Chem. 272, 168-173
57. Fukazawa, T., Reedquist, K. A., Trub, T., Soltoff, S., Panchamoorthy, G., Druker, B., Cantley, L., Shoelson, S. E., and Band, H. (1995) The SH3 domain-binding T cell tyrosyl phosphoprotein p120. Demonstration of its identity with the c-cbl protooncogene product and in vivo complexes with Fyn, Grb2, and phosphatidylinositol 3-kinase. J. Biol. Chem. 270, 19141-19150
58. Reedquist, K. A., Fukazawa, T., Panchamoorthy, G., Langdon, W. Y., Shoelson, S. E., Druker, B. J., and Band, H. (1996) Stimulation through the T cell receptor induces Cbl association with Crk proteins and the guanine nucleotide exchange protein C3G. J. Biol. Chem. 271, 8435-8442
59. Sawasdikosol, S., Chang, J. H., Pratt, J. C., Wolf, G., Shoelson, S. E., and Burakoff, S. J. (1996) Tyrosine-phosphorylated Cbl binds to Crk after T cell activation. J. Immunol. 157, 110-116
60. Andoniou, C. E., Thien, C. B., and Langdon, W. Y. (1996) The two major sites of cbl tyrosine phosphorylation in abl-transformed cells select the crkL SH2 domain. Oncogene 12, 1981-1989
61. Meng, F., and Lowell, C. A. (1998) A β 1 integrin signaling pathway involving Src-family kinases, Cbl and PI-3 kinase is required for macrophage spreading and migration. EMBO J. 17, 4391-4403
62. Grishin, A., Sinha, S., Roginskaya, V., Boyer, M. J., Gomez-Cambronero, J., Zuo, S., Kurosaki, T., Romero, G., and Corey, S. J. (2000) Involvement of Shc and Cbl-PI 3-kinase in Lyn-dependent proliferative signaling pathways for G-CSF. Oncogene 19, 97-105
63. Tezuka, T., Umemori, H., Fusaki, N., Yagi, T., Takata, M., Kurosaki, T., and Yamamoto, T. (1996) Physical and functional association of the cbl protooncogen product with an src-family protein tyrosine kinase, p53/56lyn, in the B cell antigen receptor-mediated signaling. J. Exp. Med. 183, 675-680
64. Uddin, S., Gardziola, C., Dangat, A., Yi, T., and Platanias, L. C. (1996) Interaction of the c-cbl proto-oncogene product with the Tyk-2 protein tyrosine kinase. Biochem. Biophys. Res. Commun. 225, 833-838
65. Muto, A., Watanabe, S., Itoh, T., Miyajima, A., Yokota, T., and Arai, K. (1995) Roles of the cytoplasmic domains of the alpha and β subunits of human granulocyte-macrophage colony-stimulating factor receptor. J. Allergy Clin. Immunol. 96, 1100-1114
66. Sakamaki, K., Miyajima, I., Kitamura, T., and Miyajima, A. (1992) Critical cytoplasmic domains of the common β subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation. EMBO J. 11, 3541-3549
67. Itoh, T., Liu, R., Yokota, T., Arai, K. I., and Watanabe, S. (1998) Definition of the role of tyrosine residues of the common β subunit regulating multiple signaling pathways of granulocyte-macrophage colony-stimulating factor receptor. Mol. Cell Biol. 18, 742-752
68. Martinez-Moczygemba, M., Huston, D. P., and Lei, J. T. (2007) JAK kinases control IL-5 receptor ubiquitination, degradation, and internalization. J. Leukoc. Biol. 81, 1137-1148
69. Lei, J. T., Mazumdar, T., and Martinez-Moczygemba, M. (2011) Three lysine residues in the common μ chain of the interleukin-5 receptor are required for Janus kinase (JAK)-dependent receptor ubiquitination, endocytosis, and signaling. J. Biol. Chem. 286, 40091-40103
70. Nagao, T., Oshikawa, G., Wu, N., Kurosu, T., and Miura, O. (2011) DNA damage stress and inhibition of Jak2-V617F cause its degradation and synergistically induce apoptosis through activation of GSK3β. PLoS One 6, e27397
71. Andoniou, C. E., Lill, N. L., Thien, C. B., Lupher, M. L., Jr., Ota, S., Bowtell, D. D., Scaife, R. M., Langdon, W. Y., and Band, H. (2000) The Cbl proto-oncogene product negatively regulates the Src-family tyrosine kinase Fyn by enhancing its degradation. Mol. Cell Biol. 20, 851-867
72. Bhattacharyya, S. P. (2001) Ubiquitination of Lyn-kinase in rat basophilic leukemia RBL-2H3 cells. Immunol. Lett. 75, 131-136
73. Kaabeche, K., Lemonnier, J., Le Mée, S., Caverzasio, J., and Marie, P. J. (2004) Cbl-mediated degradation of Lyn and Fyn induced by constitutive fibroblast growth factor receptor-2 activation supports osteoblast differentiation. J. Biol. Chem. 279, 36259-36267
74. Kyo, S., Sada, K., Qu, X., Maeno, K., Miah, S. M., Kawauchi-Kamata, K., and Yamamura, H. (2003) Negative regulation of Lyn protein-tyrosine kinase by c-Cbl ubiquitin-protein ligase in Fc ε RI-mediated mast cell activation. Genes Cells 8, 825-836
75. Wang, L., Rudert, W. A., Loutaev, I., Roginskaya, V., and Corey, S. J. (2002) Repression of c-Cbl leads to enhanced G-CSF Jak-STAT signaling without increased cell proliferation. Oncogene 21, 5346-5355
76. Nishizumi, H., Horikawa, K., Mlinaric-Rascan, I., and Yamamoto, T. (1998) A double-edged kinase Lyn. A positive and negative regulator for antigen receptor-mediated signals. J. Exp. Med. 187, 1343-1348
77. Dombrosky-Ferlan, P. M., and Corey, S. J. (1997) Yeast two-hybrid in vivo association of the Src kinase Lyn with the proto-oncogene product Cbl but not with the p85 subunit of PI 3-kinase. Oncogene 14, 2019-2024
78. Kotecha, N., Flores, N. J., Irish, J. M., Simonds, E. F., Sakai, D. S., Archambeault, S., Diaz-Flores, E., Coram, M., Shannon, K. M., Nolan, G. P., and Loh, M. L. (2008) Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell 14, 335-343
79. Guthridge, M. A., Powell, J. A., Barry, E. F., Stomski, F. C., McClure, B. J., Ramshaw, H., Felquer, F. A., Dottore, M., Thomas, D. T., To, B., Begley, C. G., and Lopez, A. F. (2006) Growth factor pleiotropy is controlled by a receptor Tyr/Ser motif that acts as a binary switch. EMBO J. 25, 479-489
80. Naramura, M., Nandwani, N., Gu, H., Band, V., and Band, H. (2010) Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B-cell lymphoma (Cbl) and Cbl-b in hematopoietic stem cells. Proc. Natl. Acad. Sci. U.S.A. 107, 16274-16279
81. Rathinam, C., Thien, C. B., Flavell, R. A., and Langdon, W. Y. (2010) Myeloid leukemia development in c-Cbl RING finger mutant mice is dependent on FLT3 signaling. Cancer Cell 18, 341-352
82. Thien, C. B., Blystad, F. D., Zhan, Y., Lew, A. M., Voigt, V., Andoniou, C. E., and Langdon, W. Y. (2005) Loss of c-Cbl RING finger function results in high-intensity TCR signaling and thymic deletion. EMBO J. 24, 3807-3819