KEGG   PATHWAY: pon05214
Entry
pon05214                    Pathway                                

Name
Glioma - Pongo abelii (Sumatran orangutan)
Description
Gliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), mixtures of various glial cells (for example,oligoastrocytomas) and ependymal cells (ependymomas). The most malignant form of infiltrating astrocytoma - glioblastoma multiforme (GBM) - is one of the most aggressive human cancers. GBM may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). Primary glioblastomas develop in older patients and typically show genetic alterations (EGFR amplification, p16/INK4a deletion, and PTEN mutations) at frequencies of 24-34%. Secondary glioblastomas develop in younger patients and frequently show overexpression of PDGF and CDK4 as well as p53 mutations (65%) and loss of Rb playing major roles in such transformations. Loss of PTEN has been implicated in both pathways, although it is much more common in the pathogenesis of primary GBM.
Class
Human Diseases; Cancer: specific types
Pathway map
pon05214  Glioma
pon05214

Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100455021  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100172994  TGFA; protransforming growth factor alpha precursor [KO:K08774]
100459280  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:2.7.10.1]
100440212  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
100460243  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
100431735  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
100460001  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
100444645  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
100172156  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100450941  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
100457650  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100436432  CALML5; calmodulin-like protein 5 [KO:K02183]
100436811  CALML3; calmodulin-like protein 3 [KO:K02183]
100444426  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
100172680  CALM1; calmodulin [KO:K02183]
100173214  CALM2; calmodulin [KO:K02183]
100172890  CALM3; calmodulin [KO:K02183]
100451658  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100455662  calmodulin-alpha-like [KO:K02183]
103892390  calmodulin-like [KO:K02183]
100462399  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
100432476  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X2 [KO:K08794] [EC:2.7.11.17]
100460905  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
100433531  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100172212  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
100462386  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100436747  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
100461605  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100434355  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100439900  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100451563  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100173225  SHC1; SHC-transforming protein 1 [KO:K06279]
100445042  SHC2; SHC-transforming protein 2 [KO:K17447]
100462011  SHC3; SHC-transforming protein 3 [KO:K17448]
100431574  SHC4; SHC-transforming protein 4 [KO:K17449]
100173972  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100434331  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100458733  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100459427  HRAS; GTPase HRas [KO:K02833]
100462513  KRAS; GTPase KRas isoform X1 [KO:K07827]
100174317  NRAS; GTPase NRas precursor [KO:K07828]
100431871  ARAF; serine/threonine-protein kinase A-Raf isoform X4 [KO:K08845] [EC:2.7.11.1]
100442288  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100173732  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
100446021  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100450988  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100169740  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100431824  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100432846  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100453779  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103889133  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100174298  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100173589  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100437617  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100454279  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100448114  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100442100  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100456786  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
100171828  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100461015  cyclin-dependent kinase inhibitor 2A [KO:K06621]
100171532  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
100435218  TP53; cellular tumor antigen p53 [KO:K04451]
100453682  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100171625  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100443314  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
100454924  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100462155  RB1; retinoblastoma-associated protein [KO:K06618]
100435851  E2F1; transcription factor E2F1 [KO:K17454]
100458002  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
100448297  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
100436665  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100452809  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100456437  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100450682  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100460189  bcl-2 homologous antagonist/killer [KO:K14021]
100432001  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100454099  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100443121  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Soni D, King JA, Kaye AH, Hovens CM.
  Title
Genetics of glioblastoma multiforme: mitogenic signaling and cell cycle pathways converge.
  Journal
J Clin Neurosci 12:1-5 (2005)
DOI:10.1016/j.jocn.2004.04.001
Reference
  Authors
Zhu Y, Parada LF.
  Title
The molecular and genetic basis of neurological tumours.
  Journal
Nat Rev Cancer 2:616-26 (2002)
DOI:10.1038/nrc866
Reference
  Authors
Holland EC.
  Title
Gliomagenesis: genetic alterations and mouse models.
  Journal
Nat Rev Genet 2:120-9 (2001)
DOI:10.1038/35052535
Reference
  Authors
Bansal K, Liang ML, Rutka JT.
  Title
Molecular biology of human gliomas.
  Journal
Technol Cancer Res Treat 5:185-94 (2006)
DOI:10.1177/153303460600500302
Reference
(Japanese)
  Authors
Tabuchi K (ed).
  Title
[Gliomas: Research and therapy] (In Japanese)
  Journal
Springer-Verlag Tokyo (2006)
Reference
  Authors
Kapoor GS, O'Rourke DM.
  Title
Mitogenic signaling cascades in glial tumors.
  Journal
Neurosurgery 52:1425-34; discussion 1434-5 (2003)
DOI:10.1227/01.NEU.0000065135.28143.39
Reference
  Authors
Hulleman E, Helin K.
  Title
Molecular mechanisms in gliomagenesis.
  Journal
Adv Cancer Res 94:1-27 (2005)
DOI:10.1016/S0065-230X(05)94001-3
Reference
  Authors
Schlessinger J.
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 103:211-25 (2000)
DOI:10.1016/S0092-8674(00)00114-8
Reference
PMID:9643506
  Authors
Ng HK, Lam PY.
  Title
The molecular genetics of central nervous system tumors.
  Journal
Pathology 30:196-202 (1998)
DOI:10.1080/00313029800169236
Reference
  Authors
Knobbe CB, Merlo A, Reifenberger G.
  Title
Pten signaling in gliomas.
  Journal
Neuro-oncol 4:196-211 (2002)
DOI:10.1093/neuonc/4.3.196
Related
pathway
pon04010  MAPK signaling pathway
pon04012  ErbB signaling pathway
pon04020  Calcium signaling pathway
pon04060  Cytokine-cytokine receptor interaction
pon04110  Cell cycle
pon04115  p53 signaling pathway
pon04150  mTOR signaling pathway
KO pathway
ko05214   
LinkDB

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