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Volumn 17, Issue 1, 2007, Pages 15-22

Deregulated Ras signaling in developmental disorders: new tricks for an old dog

Author keywords

[No Author keywords available]

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE KINASE; RAF PROTEIN; RAS PROTEIN;

EID: 33846207546     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gde.2006.12.004     Document Type: Review
Times cited : (107)

References (47)
  • 1
    • 0037805547 scopus 로고    scopus 로고
    • RAS oncogenes: the first 30 years
    • Malumbres M., and Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 3 (2003) 459-465
    • (2003) Nat Rev Cancer , vol.3 , pp. 459-465
    • Malumbres, M.1    Barbacid, M.2
  • 2
    • 0035936783 scopus 로고    scopus 로고
    • NF1 tumor suppressor gene function: narrowing the GAP
    • Cichowski K., and Jacks T. NF1 tumor suppressor gene function: narrowing the GAP. Cell 104 (2001) 593-604
    • (2001) Cell , vol.104 , pp. 593-604
    • Cichowski, K.1    Jacks, T.2
  • 3
    • 18444401014 scopus 로고    scopus 로고
    • Noonan syndrome and related disorders: genetics and pathogenesis
    • Tartaglia M., and Gelb B.D. Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet 6 (2005) 45-68
    • (2005) Annu Rev Genomics Hum Genet , vol.6 , pp. 45-68
    • Tartaglia, M.1    Gelb, B.D.2
  • 4
    • 27144531386 scopus 로고    scopus 로고
    • Germline mutations in HRAS proto-oncogene cause Costello syndrome
    • This study, demonstrating heterozygous mutations in H-RAS in 12 out of 13 individuals with Costello syndrome, is the first report of a germline RAS gene mutation as the cause of a human disease. Mutations alter the same amino acids that are altered in cancer.
    • Aoki Y., Niihori T., Kawame H., Kurosawa K., Ohashi H., Tanaka Y., Filocamo M., Kato K., Suzuki Y., Kure S., et al. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet 37 (2005) 1038-1040. This study, demonstrating heterozygous mutations in H-RAS in 12 out of 13 individuals with Costello syndrome, is the first report of a germline RAS gene mutation as the cause of a human disease. Mutations alter the same amino acids that are altered in cancer.
    • (2005) Nat Genet , vol.37 , pp. 1038-1040
    • Aoki, Y.1    Niihori, T.2    Kawame, H.3    Kurosawa, K.4    Ohashi, H.5    Tanaka, Y.6    Filocamo, M.7    Kato, K.8    Suzuki, Y.9    Kure, S.10
  • 5
    • 33644629727 scopus 로고    scopus 로고
    • Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome
    • This study identified eight mutations in B-RAF in 16 individuals, and two mutations in K-RAS in three individuals with cardio-facio-cutaneous syndrome. Four B-Raf and one K-Ras mutant protein activated ELK, a reporter of ERK activation, in a luciferase reporter assay in NIH3T3 cells.
    • Niihori T., Aoki Y., Narumi Y., Neri G., Cave H., Verloes A., Okamoto N., Hennekam R.C., Gillessen-Kaesbach G., Wieczorek D., et al. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet 38 (2006) 294-296. This study identified eight mutations in B-RAF in 16 individuals, and two mutations in K-RAS in three individuals with cardio-facio-cutaneous syndrome. Four B-Raf and one K-Ras mutant protein activated ELK, a reporter of ERK activation, in a luciferase reporter assay in NIH3T3 cells.
    • (2006) Nat Genet , vol.38 , pp. 294-296
    • Niihori, T.1    Aoki, Y.2    Narumi, Y.3    Neri, G.4    Cave, H.5    Verloes, A.6    Okamoto, N.7    Hennekam, R.C.8    Gillessen-Kaesbach, G.9    Wieczorek, D.10
  • 7
    • 33644622238 scopus 로고    scopus 로고
    • Germline KRAS mutations cause Noonan syndrome
    • This study identified three de novo germline K-RAS mutations in five individuals with Noonan syndrome, and one K-RAS mutation in an individual with cardio-facio-cutaneous syndrome. These mutations do not occur in cancer and encode K-Ras mutant proteins that are hyperactive relative to wild type K-Ras, but less potent than common oncogenic K-Ras. Biochemical analysis supports cell type-specific effects of these mutant proteins. This study also infers a central role for K-Ras in normal development and in the pathogenesis of Noonan syndrome.
    • Schubbert S., Zenker M., Rowe S.L., Boll S., Klein C., Bollag G., van der Burgt I., Musante L., Kalscheuer V., Wehner L.E., et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet 38 (2006) 331-336. This study identified three de novo germline K-RAS mutations in five individuals with Noonan syndrome, and one K-RAS mutation in an individual with cardio-facio-cutaneous syndrome. These mutations do not occur in cancer and encode K-Ras mutant proteins that are hyperactive relative to wild type K-Ras, but less potent than common oncogenic K-Ras. Biochemical analysis supports cell type-specific effects of these mutant proteins. This study also infers a central role for K-Ras in normal development and in the pathogenesis of Noonan syndrome.
    • (2006) Nat Genet , vol.38 , pp. 331-336
    • Schubbert, S.1    Zenker, M.2    Rowe, S.L.3    Boll, S.4    Klein, C.5    Bollag, G.6    van der Burgt, I.7    Musante, L.8    Kalscheuer, V.9    Wehner, L.E.10
  • 8
    • 33845900943 scopus 로고    scopus 로고
    • ••].
  • 9
    • 33846238382 scopus 로고    scopus 로고
    • ••] demonstrate that germline SOS1 mutations cause ∼10% of Noonan syndrome. These mutations introduce amino acid substitutions into the SOS1 protein and cluster within domains of the protein that are thought to be important in negatively regulating its guanine nucleotide exchange activity. Expression of mutant SOS1 proteins in cultured cell lines was associated with elevated levels of Ras-GTP and phosphorylated ERK, which is consistent with the idea that these mutations increase the rate of nucleotide exchange on Ras.
  • 10
    • 0027732538 scopus 로고
    • Proteins regulating Ras and its relatives
    • Boguski M., and McCormick F. Proteins regulating Ras and its relatives. Nature 366 (1993) 643-653
    • (1993) Nature , vol.366 , pp. 643-653
    • Boguski, M.1    McCormick, F.2
  • 11
    • 0037075886 scopus 로고    scopus 로고
    • GTPase activating proteins: critical regulators of intracellular signaling
    • Donovan S., Shannon K.M., and Bollag G. GTPase activating proteins: critical regulators of intracellular signaling. BBA Rev Cancer 1602 (2002) 23-45
    • (2002) BBA Rev Cancer , vol.1602 , pp. 23-45
    • Donovan, S.1    Shannon, K.M.2    Bollag, G.3
  • 12
    • 0035834388 scopus 로고    scopus 로고
    • The guanine nucleotide-binding switch in three dimensions
    • Vetter I.R., and Wittinghofer A. The guanine nucleotide-binding switch in three dimensions. Science 294 (2001) 1299-1304
    • (2001) Science , vol.294 , pp. 1299-1304
    • Vetter, I.R.1    Wittinghofer, A.2
  • 13
    • 0037264633 scopus 로고    scopus 로고
    • Targeting RAS signalling pathways in cancer therapy
    • Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3 (2003) 11-22
    • (2003) Nat Rev Cancer , vol.3 , pp. 11-22
    • Downward, J.1
  • 14
    • 33745199375 scopus 로고    scopus 로고
    • The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2
    • This study in yeast identifies a role for the kelch domain-containing proteins Gpb1 and Gpb2 in stabilizing neurofibromin homologs Ira1 and Ira2, through interaction with a carboxy-terminal region of Ira1 and Ira2 known as the GBP binding domain (GBD). The GBD is conserved between flies and mammals and is downstream of the GAP-related domain (GRD). Interaction of mammalian kelch proteins with the GBD of neurofibromin might provide a mechanism to keep Ras-GTP levels in check. Furthermore, NF1 mutations that affect the GBD might provide a mechanism by which NF1 develops.
    • Harashima T., Anderson S., Yates III J.R., and Heitman J. The kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with the yeast RasGAP neurofibromin homologs Ira1 and Ira2. Mol Cell 22 (2006) 819-830. This study in yeast identifies a role for the kelch domain-containing proteins Gpb1 and Gpb2 in stabilizing neurofibromin homologs Ira1 and Ira2, through interaction with a carboxy-terminal region of Ira1 and Ira2 known as the GBP binding domain (GBD). The GBD is conserved between flies and mammals and is downstream of the GAP-related domain (GRD). Interaction of mammalian kelch proteins with the GBD of neurofibromin might provide a mechanism to keep Ras-GTP levels in check. Furthermore, NF1 mutations that affect the GBD might provide a mechanism by which NF1 develops.
    • (2006) Mol Cell , vol.22 , pp. 819-830
    • Harashima, T.1    Anderson, S.2    Yates III, J.R.3    Heitman, J.4
  • 15
    • 33748298960 scopus 로고    scopus 로고
    • The neurofibromin GAP-related domain rescues endothelial but not neural crest development in Nf1 mice
    • Ismat F.A., Xu J., Lu M.M., and Epstein J.A. The neurofibromin GAP-related domain rescues endothelial but not neural crest development in Nf1 mice. J Clin Invest 116 (2006) 2378-2384
    • (2006) J Clin Invest , vol.116 , pp. 2378-2384
    • Ismat, F.A.1    Xu, J.2    Lu, M.M.3    Epstein, J.A.4
  • 16
    • 16844375160 scopus 로고    scopus 로고
    • Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors
    • Dasgupta B., Yi Y., Chen D.Y., Weber J.D., and Gutmann D.H. Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Cancer Res 65 (2005) 2755-2760
    • (2005) Cancer Res , vol.65 , pp. 2755-2760
    • Dasgupta, B.1    Yi, Y.2    Chen, D.Y.3    Weber, J.D.4    Gutmann, D.H.5
  • 19
    • 0038771965 scopus 로고    scopus 로고
    • The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling
    • Neel B.G., Gu H., and Pao L. The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 28 (2003) 284-293
    • (2003) Trends Biochem Sci , vol.28 , pp. 284-293
    • Neel, B.G.1    Gu, H.2    Pao, L.3
  • 20
    • 0033989423 scopus 로고    scopus 로고
    • Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps
    • O'Reilly A.M., Pluskey S., Shoelson S.E., and Neel B.G. Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps. Mol Cell Biol 20 (2000) 299-311
    • (2000) Mol Cell Biol , vol.20 , pp. 299-311
    • O'Reilly, A.M.1    Pluskey, S.2    Shoelson, S.E.3    Neel, B.G.4
  • 21
    • 24744465207 scopus 로고    scopus 로고
    • Diverse biochemical properties of Shp2 mutants: Implications for disease phenotypes
    • The authors carefully interrogated the biochemical activities of a large panel of mutant SHP-2 proteins associated with Noonan syndrome and leukemia. The results show that mutations in PTPN11 can affect not only SHP-2 basal activation but also SH2 domain binding to phosphotyrosyl ligands, and/or substrate specificity. Therefore, mutant SHP-2 proteins cause disease by multiple mechanisms, and the severity of the disease phenotype does not necessarily correlate to phosphatase activity alone.
    • Keilhack H., David F.S., McGregor M., Cantley L.C., and Neel B.G. Diverse biochemical properties of Shp2 mutants: Implications for disease phenotypes. J Biol Chem 280 (2005) 30984-30993. The authors carefully interrogated the biochemical activities of a large panel of mutant SHP-2 proteins associated with Noonan syndrome and leukemia. The results show that mutations in PTPN11 can affect not only SHP-2 basal activation but also SH2 domain binding to phosphotyrosyl ligands, and/or substrate specificity. Therefore, mutant SHP-2 proteins cause disease by multiple mechanisms, and the severity of the disease phenotype does not necessarily correlate to phosphatase activity alone.
    • (2005) J Biol Chem , vol.280 , pp. 30984-30993
    • Keilhack, H.1    David, F.S.2    McGregor, M.3    Cantley, L.C.4    Neel, B.G.5
  • 22
    • 33645280589 scopus 로고    scopus 로고
    • Inherited predispositions and hyperactive Ras in myeloid leukemogenesis
    • Lauchle J.O., Braun B.S., Loh M.L., and Shannon K. Inherited predispositions and hyperactive Ras in myeloid leukemogenesis. Pediatr Blood Cancer 46 (2006) 579-585
    • (2006) Pediatr Blood Cancer , vol.46 , pp. 579-585
    • Lauchle, J.O.1    Braun, B.S.2    Loh, M.L.3    Shannon, K.4
  • 26
    • 18244395853 scopus 로고    scopus 로고
    • Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor
    • Chan R.J., Leedy M.B., Munugalavadla V., Voorhorst C.S., Li Y., Yu M., and Kapur R. Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor. Blood 105 (2005) 3737-3742
    • (2005) Blood , vol.105 , pp. 3737-3742
    • Chan, R.J.1    Leedy, M.B.2    Munugalavadla, V.3    Voorhorst, C.S.4    Li, Y.5    Yu, M.6    Kapur, R.7
  • 28
    • 22044452124 scopus 로고    scopus 로고
    • Functional analysis of leukemia-associated PTPN11 mutations in primary hematopoietic cells
    • Schubbert S., Lieuw K., Rowe S.L., Lee C.M., Li X., Loh M.L., Clapp D.W., and Shannon K.M. Functional analysis of leukemia-associated PTPN11 mutations in primary hematopoietic cells. Blood 106 (2005) 311-317
    • (2005) Blood , vol.106 , pp. 311-317
    • Schubbert, S.1    Lieuw, K.2    Rowe, S.L.3    Lee, C.M.4    Li, X.5    Loh, M.L.6    Clapp, D.W.7    Shannon, K.M.8
  • 30
    • 33646096207 scopus 로고    scopus 로고
    • PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects
    • •] demonstrate that gain-of-function and dominant negative mutations in the same protein result in similar disease phenotypes. It is possible that LEOPARD syndrome and Noonan syndrome-associated mutant proteins act at different times in development or in specific cell types. A knock-in mouse model of LEOPARD syndrome might clarify how LEOPARD syndrome mutant proteins perturb developmental programs.
    • •] demonstrate that gain-of-function and dominant negative mutations in the same protein result in similar disease phenotypes. It is possible that LEOPARD syndrome and Noonan syndrome-associated mutant proteins act at different times in development or in specific cell types. A knock-in mouse model of LEOPARD syndrome might clarify how LEOPARD syndrome mutant proteins perturb developmental programs.
    • (2006) J Biol Chem , vol.281 , pp. 6785-6792
    • Kontaridis, M.I.1    Swanson, K.D.2    David, F.S.3    Barford, D.4    Neel, B.G.5
  • 32
    • 33646117025 scopus 로고    scopus 로고
    • Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1
    • Hanna N., Montagner A., Lee W.H., Miteva M., Vidal M., Vidaud M., Parfait B., and Raynal P. Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS Letters 580 (2006) 2477-2482
    • (2006) FEBS Letters , vol.580 , pp. 2477-2482
    • Hanna, N.1    Montagner, A.2    Lee, W.H.3    Miteva, M.4    Vidal, M.5    Vidaud, M.6    Parfait, B.7    Raynal, P.8
  • 33
    • 30144434094 scopus 로고    scopus 로고
    • HRAS mutations in Costello syndrome: detection of constitutional activating mutations in codon 12 and 13 and loss of wild-type allele in malignancy
    • Estep A.L., Tidyman W.E., Teitell M.A., Cotter P.D., and Rauen K.A. HRAS mutations in Costello syndrome: detection of constitutional activating mutations in codon 12 and 13 and loss of wild-type allele in malignancy. Am J Med Genet A 140 (2006) 8-16
    • (2006) Am J Med Genet A , vol.140 , pp. 8-16
    • Estep, A.L.1    Tidyman, W.E.2    Teitell, M.A.3    Cotter, P.D.4    Rauen, K.A.5
  • 38
    • 12144289677 scopus 로고    scopus 로고
    • Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    • The authors analyzed a panel of cancer-associated B-Raf mutant proteins. Although most mutants display elevated kinase activity towards MEK in vitro, some mutants are impaired. Interestingly, the kinase-impaired mutants activate ERK in vivo in COS and Xenopus cells. The authors describe a novel mechanism by which kinase-impaired mutant B-Raf proteins signal to ERK by activating c-Raf. This is also the first description of the three-dimensional structure of B-Raf, enabling structural analysis of individual mutations.
    • Wan P.T., Garnett M.J., Roe S.M., Lee S., Niculescu-Duvaz D., Good V.M., Jones C.M., Marshall C.J., Springer C.J., Barford D., et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116 (2004) 855-867. The authors analyzed a panel of cancer-associated B-Raf mutant proteins. Although most mutants display elevated kinase activity towards MEK in vitro, some mutants are impaired. Interestingly, the kinase-impaired mutants activate ERK in vivo in COS and Xenopus cells. The authors describe a novel mechanism by which kinase-impaired mutant B-Raf proteins signal to ERK by activating c-Raf. This is also the first description of the three-dimensional structure of B-Raf, enabling structural analysis of individual mutations.
    • (2004) Cell , vol.116 , pp. 855-867
    • Wan, P.T.1    Garnett, M.J.2    Roe, S.M.3    Lee, S.4    Niculescu-Duvaz, D.5    Good, V.M.6    Jones, C.M.7    Marshall, C.J.8    Springer, C.J.9    Barford, D.10
  • 39
    • 33644829154 scopus 로고    scopus 로고
    • Stops along the RAS pathway in human genetic disease
    • Bentires-Alj M., Kontaridis M.I., and Neel B.G. Stops along the RAS pathway in human genetic disease. Nat Med 12 (2006) 283-285
    • (2006) Nat Med , vol.12 , pp. 283-285
    • Bentires-Alj, M.1    Kontaridis, M.I.2    Neel, B.G.3
  • 40
    • 3142620903 scopus 로고    scopus 로고
    • Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia
    • Tartaglia M., Martinelli S., Cazzaniga G., Cordeddu V., Iavarone I., Spinelli M., Palmi C., Carta C., Pession A., Arico M., et al. Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood 104 (2004) 307-313
    • (2004) Blood , vol.104 , pp. 307-313
    • Tartaglia, M.1    Martinelli, S.2    Cazzaniga, G.3    Cordeddu, V.4    Iavarone, I.5    Spinelli, M.6    Palmi, C.7    Carta, C.8    Pession, A.9    Arico, M.10
  • 46
    • 33644864788 scopus 로고    scopus 로고
    • Compartmentalized Ras/MAPK signaling
    • Mor A., and Philips M.R. Compartmentalized Ras/MAPK signaling. Annu Rev Immunol 24 (2006) 771-800
    • (2006) Annu Rev Immunol , vol.24 , pp. 771-800
    • Mor, A.1    Philips, M.R.2
  • 47
    • 33344475413 scopus 로고    scopus 로고
    • Differential modification of Ras proteins by ubiquitination
    • Jura N., Scotto-Lavino E., Sobczyk A., and Bar-Sagi D. Differential modification of Ras proteins by ubiquitination. Mol Cell 21 (2006) 679-687
    • (2006) Mol Cell , vol.21 , pp. 679-687
    • Jura, N.1    Scotto-Lavino, E.2    Sobczyk, A.3    Bar-Sagi, D.4


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.