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Protein: GRB2_HUMAN [Homo sapiens]
from Cancer Cell Map, MINT, IntAct, BioGRID, NCI / Nature Pathway Interaction Database, IMID [65 pathways, 1013 interactions]
Growth factor receptor-bound protein 2
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Protein: PIP3 [Human]
from IMID [173 interactions]
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Protein: SRC_HUMAN [Homo sapiens]
from Cancer Cell Map, HPRD, MINT, IntAct, HumanCyc, BioGRID, NCI / Nature Pathway Interaction Database, IMID [76 pathways, 865 interactions]
Proto-oncogene tyrosine-protein kinase Src
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Protein: EGFR_HUMAN [Homo sapiens]
from Cancer Cell Map, HPRD, MINT, Reactome, IntAct, HumanCyc, BioGRID, NCI / Nature Pathway Interaction Database, IMID [49 pathways, 835 interactions]
Epidermal growth factor receptor
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Summary: FUNCTION: Receptor for EGF, but also for other members of the EGF family, as TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30 and vaccinia virus growth factor. Is involved in the control of cell growth and differentiation. Phosphorylates MUC1 in breast cancer cells and increases the interaction of MUC1 with SRC and CTNNB1/beta-catenin.
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Protein: NCK1_HUMAN [Homo sapiens]
from Cancer Cell Map, HPRD, MINT, Reactome, IntAct, BioGRID, NCI / Nature Pathway Interaction Database, IMID [50 pathways, 829 interactions]
Cytoplasmic protein NCK1
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Summary: FUNCTION: Adapter protein which associates with tyrosine- phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2.
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Protein: CTNB1_HUMAN [Homo sapiens]
from HPRD, MINT, IntAct, BioGRID, NCI / Nature Pathway Interaction Database, IMID [51 pathways, 678 interactions]
Catenin beta-1
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Summary: FUNCTION: Involved in the regulation of cell adhesion. The majority of beta-catenin is localized to the cell membrane and is part of E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton.
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Protein: FYN_HUMAN [Homo sapiens]
from Cancer Cell Map, HPRD, MINT, Reactome, IntAct, HumanCyc, BioGRID, NCI / Nature Pathway Interaction Database, IMID [39 pathways, 812 interactions]
Tyrosine-protein kinase Fyn
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Summary: FUNCTION: Implicated in the control of cell growth. Plays a role in the regulation of intracellular calcium levels, with isoform 2 showing the greater ability to mobilize cytoplasmic calcium in comparison to isoform 1. Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension. Blocks axon outgrowth and attraction induced by NTN1 by phosphorylating its receptor DDC. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. COFACTOR: Manganese.
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Protein: MDM2_HUMAN [Homo sapiens]
from Cancer Cell Map, MINT, Reactome, IntAct, BioGRID, NCI / Nature Pathway Interaction Database, IMID [114 pathways, 603 interactions]
E3 ubiquitin-protein ligase Mdm2
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Summary: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of TP53/p53. Promotes proteasome-dependent ubiquitin- independent degradation of retinoblastoma RB1 protein.
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Protein: NFKB1_HUMAN [Homo sapiens]
from Cancer Cell Map, HPRD, MINT, Reactome, IntAct, BioGRID, NCI / Nature Pathway Interaction Database, IMID [72 pathways, 566 interactions]
Nuclear factor NF-kappa-B p105 subunit
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Summary: FUNCTION: NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post- translationally. p50 binds to the kappa-B consensus sequence 5'- GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.
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Protein: RB_HUMAN [Homo sapiens]
from Cancer Cell Map, HPRD, MINT, Reactome, IntAct, BioGRID, NCI / Nature Pathway Interaction Database, IMID [57 pathways, 602 interactions]
Retinoblastoma-associated protein
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Summary: FUNCTION: Key regulator of entry into cell division that acts as a tumor suppressor. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.
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