| Growth factor receptor-bound protein 2 |
PDB rendering based on 1gri. |
| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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1AZE, 1BM2, 1BMB, 1CJ1, 1FHS, 1FYR, 1GCQ, 1GFC, 1GFD, 1GHU, 1GRI, 1IO6, 1JYQ, 1JYR, 1JYU, 1QG1, 1TZE, 1X0N, 1ZFP, 2AOA, 2AOB, 2H46, 2H5K, 2HUW, 2VVK, 2VWF, 2W0Z, 3C7I, 3IMD, 3IMJ, 3IN7, 3IN8, 3KFJ, 3MXC, 3MXY, 3N7Y, 3N84, 3N8M, 3OV1, 3OVE, 3S8L, 3S8N, 3S8O, 3WA4
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| Identifiers |
| Symbols |
GRB2 ; ASH; EGFRBP-GRB2; Grb3-3; MST084; MSTP084; NCKAP2 |
| External IDs |
OMIM: 108355 MGI: 95805 HomoloGene: 1576 ChEMBL: 3663 GeneCards: GRB2 Gene |
| Gene ontology |
| Molecular function |
• phosphotyrosine binding
• SH3/SH2 adaptor activity
• epidermal growth factor receptor binding
• neurotrophin TRKA receptor binding
• protein binding
• SH3 domain binding
• protein kinase binding
• protein phosphatase binding
• identical protein binding
• insulin receptor substrate binding
• poly(A) RNA binding
• ephrin receptor binding
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| Cellular component |
• nucleus
• cytoplasm
• endosome
• Golgi apparatus
• cytosol
• plasma membrane
• COP9 signalosome
• vesicle membrane
• extracellular vesicular exosome
• Grb2-EGFR complex
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| Biological process |
• epidermal growth factor receptor signaling pathway
• Ras protein signal transduction
• cell-cell signaling
• axon guidance
• aging
• blood coagulation
• insulin receptor signaling pathway
• fibroblast growth factor receptor signaling pathway
• positive regulation of signal transduction
• viral process
• platelet activation
• positive regulation of actin filament polymerization
• T cell costimulation
• receptor internalization
• Fc-epsilon receptor signaling pathway
• Fc-gamma receptor signaling pathway involved in phagocytosis
• negative regulation of epidermal growth factor receptor signaling pathway
• signal transduction in response to DNA damage
• regulation of MAPK cascade
• innate immune response
• neurotrophin TRK receptor signaling pathway
• phosphatidylinositol-mediated signaling
• anatomical structure formation involved in morphogenesis
• leukocyte migration
• protein heterooligomerization
• branching involved in labyrinthine layer morphogenesis
• cellular response to ionizing radiation
• positive regulation of reactive oxygen species metabolic process
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| Sources: Amigo / QuickGO |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
2885 |
14784 |
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| Ensembl |
ENSG00000177885 |
ENSMUSG00000059923 |
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| UniProt |
P62993 |
Q60631 |
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| RefSeq (mRNA) |
NM_002086 |
NM_008163 |
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| RefSeq (protein) |
NP_002077 |
NP_032189 |
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| Location (UCSC) |
Chr 17:
73.31 – 73.4 Mb |
Chr 11:
115.64 – 115.71 Mb |
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| PubMed search |
[1] |
[2] |
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Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.[1][2]
The protein encoded by this gene binds receptors such as the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the sem-5 gene of Caenorhabditis elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.[3]
Contents
- 1 Function and expression
- 2 Domains
- 3 Interactions
- 4 See also
- 5 References
- 6 Further reading
- 7 External links
Function and expression
Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types, and so it is not surprising that a targeted gene disruption of Grb2 in mouse is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction.
Domains
The SH2 domain of Grb2 binds to phosphorylated tyrosine-containing peptides on receptors or scaffold proteins with a preference for pY-X-N-X, where X is generally a hydrophobic residue such as valine (see [3]).
The N-terminal SH3 domain binds to proline-rich peptides and can bind to the Ras-guanine exchange factor SOS.
The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1.[4]
Interactions
Grb2 has been shown to interact with Arachidonate 5-lipoxygenase,[5][6] Lymphocyte cytosolic protein 2,[7][8][9][10][11] GAB2,[12][13][14] B-cell linker,[15][16][17][18] Abl gene,[19][20] CD28,[21][22] FRS2,[23][24][25][26] Mitogen-activated protein kinase 9,[27][28] CD22,[29][30] NEU3,[31] ETV6,[12] MAP2,[32][33] Dock180,[34][35] PIK3R1,[36][37] SH2B1,[38][39] CRK,[40][41][42] GAB1,[7][43][44] MST1R,[45][46] DNM1,[47][48] Huntingtin,[49] Src,[50][51] Beta-2 adrenergic receptor,[52] VAV2,[53][54] ADAM15,[55] RAPGEF1,[56][57] VAV1,[58][59][60][61] HER2/neu,[54][62][63] Epidermal growth factor receptor,[2][43][53][62][64][65][66][67][68][69] PDGFRB,[69][70][71] PTK2,[72][73][74][75][76] Erythropoietin receptor,[77][78] Linker of activated T cells,[79][80][81] Dystroglycan,[82] SH3KBP1,[83][84] Granulocyte colony-stimulating factor receptor,[85] DCTN1,[86] CDKN1B,[87] Colony stimulating factor 1 receptor,[88] EPH receptor A2,[89] KHDRBS1,[43][90][91] RET proto-oncogene,[92][93] PLCG1,[94][95][96] TrkA,[97][98] PRKAR1A,[66] Janus kinase 2,[99][100] MUC1,[101] CD117,[78][102][103] Fas ligand,[104][105] Janus kinase 1,[100][106] VAV3,[53][107] BCAR1,[73][108] PTPN1,[109][110] INPP5D,[111] ITK,[112][113] SHC1,[51][53][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] PTPN12,[133] C-Met,[134][135] PTPN11,[71][85][127][136][137][138][139][140][141] Glycoprotein 130,[61] PTPN6,[51][136][142] Syk,[51][136] MAP4K1,[143][144][145][146] Wiskott-Aldrich syndrome protein,[147][148] NCKIPSD,[149][150] PTPRA,[151][152][153] BCR gene,[12][115][154][155][156][157] CBLB,[158][159][160] Cbl gene,[9][24][51][90][124][158][161][162][163][164][165][166][167] SOS1,[8][24][42][43][48][51][53][60][68][90][95][101][115][122][124][131][168][169][170][171][172] IRS1,[100][114][173] TNK2,[116][174] MED28,[175] MAP3K1[176] and HNRNPC.[177]
See also
References
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- ^ a b Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J (August 1992). "The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling". Cell 70 (3): 431–42. doi:10.1016/0092-8674(92)90167-B. PMID 1322798.
- ^ "Entrez Gene: GRB2 growth factor receptor-bound protein 2".
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- ^ a b Lewitzky, M; Kardinal C; Gehring N H; Schmidt E K; Konkol B; Eulitz M; Birchmeier W; Schaeper U; Feller S M (Mar 2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene (England) 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. ISSN 0950-9232. PMID 11314042.
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- ^ Yokote, K; Mori S; Hansen K; McGlade J; Pawson T; Heldin C H; Claesson-Welsh L (May 1994). "Direct interaction between Shc and the platelet-derived growth factor beta-receptor". J. Biol. Chem. (UNITED STATES) 269 (21): 15337–43. ISSN 0021-9258. PMID 8195171.
- ^ a b Zhang, S; Mantel C; Broxmeyer H E (Mar 1999). "Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells". J. Leukoc. Biol. (UNITED STATES) 65 (3): 372–80. ISSN 0741-5400. PMID 10080542.
- ^ Lazar, D F; Knez J J; Medof M E; Cuatrecasas P; Saltiel A R (Oct 1994). "Stimulation of glycogen synthesis by insulin in human erythroleukemia cells requires the synthesis of glycosyl-phosphatidylinositol". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 91 (21): 9665–9. doi:10.1073/pnas.91.21.9665. ISSN 0027-8424. PMC 44877. PMID 7524086.
- ^ VanderKuur, J; Allevato G; Billestrup N; Norstedt G; Carter-Su C (Mar 1995). "Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2". J. Biol. Chem. (UNITED STATES) 270 (13): 7587–93. doi:10.1074/jbc.270.13.7587. ISSN 0021-9258. PMID 7535773.
- ^ Kanai, M; Göke M; Tsunekawa S; Podolsky D K (Mar 1997). "Signal transduction pathway of human fibroblast growth factor receptor 3. Identification of a novel 66-kDa phosphoprotein". J. Biol. Chem. (UNITED STATES) 272 (10): 6621–8. doi:10.1074/jbc.272.10.6621. ISSN 0021-9258. PMID 9045692.
- ^ a b Spivak-Kroizman, T; Mohammadi M; Hu P; Jaye M; Schlessinger J; Lax I (May 1994). "Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells". J. Biol. Chem. (UNITED STATES) 269 (20): 14419–23. ISSN 0021-9258. PMID 7514169.
- ^ Giordano, V; De Falco G; Chiari R; Quinto I; Pelicci P G; Bartholomew L; Delmastro P; Gadina M; Scala G (May 1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. (UNITED STATES) 158 (9): 4097–103. ISSN 0022-1767. PMID 9126968.
- ^ Charest, A; Wagner J; Kwan M; Tremblay M L (Apr 1997). "Coupling of the murine protein tyrosine phosphatase PEST to the epidermal growth factor (EGF) receptor through a Src homology 3 (SH3) domain-mediated association with Grb2". Oncogene (ENGLAND) 14 (14): 1643–51. doi:10.1038/sj.onc.1201008. ISSN 0950-9232. PMID 9135065.
- ^ Ponzetto, C; Zhen Z; Audero E; Maina F; Bardelli A; Basile M L; Giordano S; Narsimhan R; Comoglio P (Jun 1996). "Specific uncoupling of GRB2 from the Met receptor. Differential effects on transformation and motility". J. Biol. Chem. (UNITED STATES) 271 (24): 14119–23. doi:10.1074/jbc.271.24.14119. ISSN 0021-9258. PMID 8662889.
- ^ Liang, Q; Mohan R R; Chen L; Wilson S E (Jul 1998). "Signaling by HGF and KGF in corneal epithelial cells: Ras/MAP kinase and Jak-STAT pathways". Invest. Ophthalmol. Vis. Sci. (UNITED STATES) 39 (8): 1329–38. ISSN 0146-0404. PMID 9660480.
- ^ a b c Ganju, R K; Brubaker S A; Chernock R D; Avraham S; Groopman J E (Jun 2000). "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". J. Biol. Chem. (UNITED STATES) 275 (23): 17263–8. doi:10.1074/jbc.M000689200. ISSN 0021-9258. PMID 10747947.
- ^ Bennett, A M; Tang T L; Sugimoto S; Walsh C T; Neel B G (Jul 1994). "Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 91 (15): 7335–9. doi:10.1073/pnas.91.15.7335. ISSN 0027-8424. PMC 44394. PMID 8041791.
- ^ Yin, T; Shen R; Feng G S; Yang Y C (Jan 1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. (UNITED STATES) 272 (2): 1032–7. doi:10.1074/jbc.272.2.1032. ISSN 0021-9258. PMID 8995399.
- ^ Tang, H; Zhao Z J; Huang X Y; Landon E J; Inagami T (Apr 1999). "Fyn kinase-directed activation of SH2 domain-containing protein-tyrosine phosphatase SHP-2 by Gi protein-coupled receptors in Madin-Darby canine kidney cells". J. Biol. Chem. (UNITED STATES) 274 (18): 12401–7. doi:10.1074/jbc.274.18.12401. ISSN 0021-9258. PMID 10212213.
- ^ Hadari, Y R; Kouhara H; Lax I; Schlessinger J (Jul 1998). "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation". Mol. Cell. Biol. (UNITED STATES) 18 (7): 3966–73. ISSN 0270-7306. PMC 108981. PMID 9632781.
- ^ Wong, L; Johnson G R (Aug 1996). "Epidermal growth factor induces coupling of protein-tyrosine phosphatase 1D to GRB2 via the COOH-terminal SH3 domain of GRB2". J. Biol. Chem. (UNITED STATES) 271 (35): 20981–4. doi:10.1074/jbc.271.35.20981. ISSN 0021-9258. PMID 8702859.
- ^ Kon-Kozlowski, M; Pani G; Pawson T; Siminovitch K A (Feb 1996). "The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells". J. Biol. Chem. (UNITED STATES) 271 (7): 3856–62. doi:10.1074/jbc.271.7.3856. ISSN 0021-9258. PMID 8632004.
- ^ Oehrl, W; Kardinal C; Ruf S; Adermann K; Groffen J; Feng G S; Blenis J; Tan T H; Feller S M (Oct 1998). "The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins". Oncogene (ENGLAND) 17 (15): 1893–901. doi:10.1038/sj.onc.1202108. ISSN 0950-9232. PMID 9788432.
- ^ Anafi, M; Kiefer F; Gish G D; Mbamalu G; Iscove N N; Pawson T (Oct 1997). "SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1". J. Biol. Chem. (UNITED STATES) 272 (44): 27804–11. doi:10.1074/jbc.272.44.27804. ISSN 0021-9258. PMID 9346925.
- ^ Ling, P; Yao Z; Meyer C F; Wang X S; Oehrl W; Feller S M; Tan T H (Feb 1999). "Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-Jun N-terminal kinase". Mol. Cell. Biol. (UNITED STATES) 19 (2): 1359–68. ISSN 0270-7306. PMC 116064. PMID 9891069.
- ^ Ling, P; Meyer C F; Redmond L P; Shui J W; Davis B; Rich R R; Hu M C; Wange R L; Tan T H (Jun 2001). "Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling". J. Biol. Chem. (United States) 276 (22): 18908–14. doi:10.1074/jbc.M101485200. ISSN 0021-9258. PMID 11279207.
- ^ Banin, S; Truong O; Katz D R; Waterfield M D; Brickell P M; Gout I (Aug 1996). "Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases". Curr. Biol. (ENGLAND) 6 (8): 981–8. doi:10.1016/S0960-9822(02)00642-5. ISSN 0960-9822. PMID 8805332.
- ^ She, H Y; Rockow S; Tang J; Nishimura R; Skolnik E Y; Chen M; Margolis B; Li W (Sep 1997). "Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells". Mol. Biol. Cell (UNITED STATES) 8 (9): 1709–21. doi:10.1091/mbc.8.9.1709. ISSN 1059-1524. PMC 305731. PMID 9307968.
- ^ Satoh, S; Tominaga T (Oct 2001). "mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation". J. Biol. Chem. (United States) 276 (42): 39290–4. doi:10.1074/jbc.M107026200. ISSN 0021-9258. PMID 11509578.
- ^ Fukuoka, M; Suetsugu S; Miki H; Fukami K; Endo T; Takenawa T (Feb 2001). "A novel neural Wiskott-Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42". J. Cell Biol. (United States) 152 (3): 471–82. doi:10.1083/jcb.152.3.471. ISSN 0021-9525. PMC 2196001. PMID 11157975.
- ^ den Hertog, J; Hunter T (Jun 1996). "Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the SH2 and C-terminal SH3 domains". EMBO J. (ENGLAND) 15 (12): 3016–27. ISSN 0261-4189. PMC 450243. PMID 8670803.
- ^ den Hertog, J; Tracy S; Hunter T (Jul 1994). "Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo". EMBO J. (ENGLAND) 13 (13): 3020–32. ISSN 0261-4189. PMC 395191. PMID 7518772.
- ^ Zheng, Xin-Min; Resnick Ross J; Shalloway David (Jun 2002). "Mitotic activation of protein-tyrosine phosphatase alpha and regulation of its Src-mediated transforming activity by its sites of protein kinase C phosphorylation". J. Biol. Chem. (United States) 277 (24): 21922–9. doi:10.1074/jbc.M201394200. ISSN 0021-9258. PMID 11923305.
- ^ Million, R P; Van Etten R A (Jul 2000). "The Grb2 binding site is required for the induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase". Blood (UNITED STATES) 96 (2): 664–70. ISSN 0006-4971. PMID 10887132.
- ^ Bai, R Y; Jahn T; Schrem S; Munzert G; Weidner K M; Wang J Y; Duyster J (Aug 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene (ENGLAND) 17 (8): 941–8. doi:10.1038/sj.onc.1202024. ISSN 0950-9232. PMID 9747873.
- ^ Ma, G; Lu D; Wu Y; Liu J; Arlinghaus R B (May 1997). "Bcr phosphorylated on tyrosine 177 binds Grb2". Oncogene (ENGLAND) 14 (19): 2367–72. doi:10.1038/sj.onc.1201053. ISSN 0950-9232. PMID 9178913.
- ^ Maru, Y; Peters K L; Afar D E; Shibuya M; Witte O N; Smithgall T E (Feb 1995). "Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS". Mol. Cell. Biol. (UNITED STATES) 15 (2): 835–42. ISSN 0270-7306. PMC 231961. PMID 7529874.
- ^ a b Ettenberg, S A; Keane M M; Nau M M; Frankel M; Wang L M; Pierce J H; Lipkowitz S (Mar 1999). "cbl-b inhibits epidermal growth factor receptor signaling". Oncogene (ENGLAND) 18 (10): 1855–66. doi:10.1038/sj.onc.1202499. ISSN 0950-9232. PMID 10086340.
- ^ Lavagna-Sévenier, C; Marchetto S; Birnbaum D; Rosnet O (Jun 1998). "The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells". J. Biol. Chem. (UNITED STATES) 273 (24): 14962–7. doi:10.1074/jbc.273.24.14962. ISSN 0021-9258. PMID 9614102.
- ^ Elly, C; Witte S; Zhang Z; Rosnet O; Lipkowitz S; Altman A; Liu Y C (Feb 1999). "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation". Oncogene (ENGLAND) 18 (5): 1147–56. doi:10.1038/sj.onc.1202411. ISSN 0950-9232. PMID 10022120.
- ^ Jain, S K; Langdon W Y; Varticovski L (May 1997). "Tyrosine phosphorylation of p120cbl in BCR/abl transformed hematopoietic cells mediates enhanced association with phosphatidylinositol 3-kinase". Oncogene (ENGLAND) 14 (18): 2217–28. doi:10.1038/sj.onc.1201049. ISSN 0950-9232. PMID 9174058.
- ^ Robertson, H; Langdon W Y; Thien C B; Bowtell D D (Nov 1997). "A c-Cbl yeast two hybrid screen reveals interactions with 14-3-3 isoforms and cytoskeletal components". Biochem. Biophys. Res. Commun. (UNITED STATES) 240 (1): 46–50. doi:10.1006/bbrc.1997.7608. ISSN 0006-291X. PMID 9367879.
- ^ Donovan, J A; Wange R L; Langdon W Y; Samelson L E (Sep 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. (UNITED STATES) 269 (37): 22921–4. ISSN 0021-9258. PMID 8083187.
- ^ Gesbert, F; Garbay C; Bertoglio J (Feb 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. (UNITED STATES) 273 (7): 3986–93. doi:10.1074/jbc.273.7.3986. ISSN 0021-9258. PMID 9461587.
- ^ 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 (ENGLAND) 14 (19): 2331–8. doi:10.1038/sj.onc.1201074. ISSN 0950-9232. PMID 9178909.
- ^ Odai, H; Sasaki K; Iwamatsu A; Nakamoto T; Ueno H; Yamagata T; Mitani K; Yazaki Y; Hirai H (Apr 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 (UNITED STATES) 89 (8): 2745–56. ISSN 0006-4971. PMID 9108392.
- ^ Ng, Cherlyn; Jackson Rebecca A; Buschdorf Jan P; Sun Qingxiang; Guy Graeme R; Sivaraman J (Mar 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. (England) 27 (5): 804–16. doi:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061.
- ^ Li, N; Batzer A; Daly R; Yajnik V; Skolnik E; Chardin P; Bar-Sagi D; Margolis B; Schlessinger J (May 1993). "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature (ENGLAND) 363 (6424): 85–8. doi:10.1038/363085a0. ISSN 0028-0836. PMID 8479541.
- ^ Reif, K; Buday L; Downward J; Cantrell D A (May 1994). "SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases". J. Biol. Chem. (UNITED STATES) 269 (19): 14081–7. ISSN 0021-9258. PMID 8188688.
- ^ D'Angelo, G; Martini J F; Iiri T; Fantl W J; Martial J; Weiner R I (May 1999). "16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells". Mol. Endocrinol. (UNITED STATES) 13 (5): 692–704. doi:10.1210/me.13.5.692. ISSN 0888-8809. PMID 10319320.
- ^ Tong, X K; Hussain N K, de Heuvel E, Kurakin A, Abi-Jaoude E, Quinn C C, Olson M F, Marais R, Baranes D, Kay B K, McPherson P S (Mar 2000). "The endocytic protein intersectin is a major binding partner for the Ras exchange factor mSos1 in rat brain". EMBO J. (ENGLAND) 19 (6): 1263–71. doi:10.1093/emboj/19.6.1263. ISSN 0261-4189. PMC 305667. PMID 10716926.
- ^ Chin, H; Saito T; Arai A; Yamamoto K; Kamiyama R; Miyasaka N; Miura O (Oct 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. (UNITED STATES) 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. ISSN 0006-291X. PMID 9344843.
- ^ Morrison, Kevin B; Tognon Cristina E; Garnett Mathew J; Deal Cheri; Sorensen Poul H B (Aug 2002). "ETV6-NTRK3 transformation requires insulin-like growth factor 1 receptor signaling and is associated with constitutive IRS-1 tyrosine phosphorylation". Oncogene (England) 21 (37): 5684–95. doi:10.1038/sj.onc.1205669. ISSN 0950-9232. PMID 12173038.
- ^ Kato-Stankiewicz, J; Ueda S; Kataoka T; Kaziro Y; Satoh T (Jun 2001). "Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner". Biochem. Biophys. Res. Commun. (United States) 284 (2): 470–7. doi:10.1006/bbrc.2001.5004. ISSN 0006-291X. PMID 11394904.
- ^ Wiederhold, Thorsten; Lee Ming-Fen; James Marianne; Neujahr Ralph; Smith Nicole; Murthy Anita; Hartwig John; Gusella James F; Ramesh Vijaya (Nov 2004). "Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2". Oncogene (England) 23 (54): 8815–25. doi:10.1038/sj.onc.1208110. ISSN 0950-9232. PMID 15467741.
- ^ Pomérance, M; Multon M C; Parker F; Venot C; Blondeau J P; Tocqué B; Schweighoffer F (Sep 1998). "Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor". J. Biol. Chem. (UNITED STATES) 273 (38): 24301–4. doi:10.1074/jbc.273.38.24301. ISSN 0021-9258. PMID 9733714.
- ^ Romero, F; Ramos-Morales F; Domínguez A; Rios R M; Schweighoffer F; Tocqué B; Pintor-Toro J A; Fischer S; Tortolero M (Mar 1998). "Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear ribonucleoprotein C, and these interactions are modulated by poly(U) RNA". J. Biol. Chem. (UNITED STATES) 273 (13): 7776–81. doi:10.1074/jbc.273.13.7776. ISSN 0021-9258. PMID 9516488.
Further reading
- Colledge M, Froehner SC (1998). "Interaction between the nicotinic acetylcholine receptor and Grb2. Implications for signaling at the neuromuscular junction.". Ann. N. Y. Acad. Sci. 841: 17–27. doi:10.1111/j.1749-6632.1998.tb10907.x. PMID 9668219.
- Ramesh N, Antón IM, Martínez-Quiles N, Geha RS (1999). "Waltzing with WASP.". Trends Cell Biol. 9 (1): 15–9. doi:10.1016/S0962-8924(98)01411-1. PMID 10087612.
- O'Sullivan E, Kinnon C, Brickell P (1999). "Wiskott-Aldrich syndrome protein, WASP.". Int. J. Biochem. Cell Biol. 31 (3–4): 383–7. doi:10.1016/S1357-2725(98)00118-6. PMID 10224664.
- Schlaepfer DD, Hauck CR, Sieg DJ (1999). "Signaling through focal adhesion kinase.". Prog. Biophys. Mol. Biol. 71 (3–4): 435–78. doi:10.1016/S0079-6107(98)00052-2. PMID 10354709.
- Vidal M, Liu WQ, Gril B, et al. (2004). "[Design of new anti-tumor agents interrupting deregulated signaling pathways induced by tyrosine kinase proteins. Inhibition of protein-protein interaction involving Grb2]". J. Soc. Biol. 198 (2): 133–7. PMID 15368963.
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PDB gallery
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1aze: NMR STRUCTURE OF THE COMPLEX BETWEEN THE C32S-Y7V MUTANT OF THE NSH3 DOMAIN OF GRB2 WITH A PEPTIDE FROM SOS, 10 STRUCTURES
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1bm2: GRB2-SH2 DOMAIN IN COMPLEX WITH CYCLO-[N-ALPHA-ACETYL-L-THI ALYSYL-O-PHOSPHOTYROSYL-VALYL-ASPARAGYL-VALYL-PROLYL] (PKF273-791)
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1bmb: GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)
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1cj1: GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVE
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1fhs: THE THREE-DIMENSIONAL SOLUTION STRUCTURE OF THE SRC HOMOLOGY DOMAIN-2 OF THE GROWTH FACTOR RECEPTOR BOUND PROTEIN-2, NMR, 18 STRUCTURES
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1fyr: DIMER FORMATION THROUGH DOMAIN SWAPPING IN THE CRYSTAL STRUCTURE OF THE GRB2-SH2 AC-PYVNV COMPLEX
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1gbq: SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, MINIMIZED AVERAGE STRUCTURE
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1gbr: ORIENTATION OF PEPTIDE FRAGMENTS FROM SOS PROTEINS BOUND TO THE N-TERMINAL SH3 DOMAIN OF GRB2 DETERMINED BY NMR SPECTROSCOPY
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1gcq: CRYSTAL STRUCTURE OF VAV AND GRB2 SH3 DOMAINS
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1gfc: SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2
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1gfd: SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2
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1ghu: NMR solution structure of growth factor receptor-bound protein 2 (GRB2) SH2 domain, 24 structures
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1io6: GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2 (GRB2) C-TERMINAL SH3 DOMAIN COMPLEXED WITH A LIGAND PEPTIDE (NMR, MINIMIZED MEAN STRUCTURE)
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1jyq: Xray Structure of Grb2 SH2 Domain Complexed with a Highly Affine Phospho Peptide
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1jyr: Xray Structure of Grb2 SH2 Domain Complexed with a Phosphorylated Peptide
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1jyu: Xray Structure of Grb2 SH2 Domain
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1qg1: GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN COMPLEXED WITH AN SHC-DERIVED PEPTIDE
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1tze: SIGNAL TRANSDUCTION ADAPTOR GROWTH FACTOR, GRB2 SH2 DOMAIN COMPLEXED WITH PHOSPHOTYROSYL HEPTAPEPTIDE LYS-PRO-PHE-PTYR-VAL-ASN-VAL-NH2 (KFPPYVNC-NH2)
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1x0n: NMR structure of growth factor receptor binding protein SH2 domain complexed with the inhibitor
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1zfp: GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PENTAPEPTIDE
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2aoa: Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain
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2aob: Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain
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2gbq: SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, 15 STRUCTURES
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2h46: Native domain-swapped dimer crystal structure of the Grb2 SH2 domain
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2h5k: Crystal Structure of Complex Between the Domain-Swapped Dimeric Grb2 SH2 Domain and Shc-Derived Ligand, Ac-NH-pTyr-Val-Asn-NH2
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2huw: X-ray crystal structure of the Grb2 SH2 domain complexed to a constrained and cyclopropane-derived ligand
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3gbq: SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, MINIMIZED AVERAGE STRUCTURE
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4gbq: SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, 15 STRUCTURES
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External links
- GRB2 Adaptor Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
- The Grb2 protein page on The SH2 Website
- GeneCards entry for Grb2
- Human Protein Resource Database entry for Grb2
- Grb2 information on iHOP (Information Hyperlinked over Proteins)
- GRB2 Info with links in the Cell Migration Gateway
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Cell signaling: carrier proteins: signal transducing adaptor proteins
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| JAK-STAT |
- see JAK-STAT signaling pathway
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| Growth factor receptor-bound protein |
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| Other |
- 14-3-3
- Caveolin
- Cortactin
- Death-inducing signaling complex
- Paxillin
- MYD88
- SMAD
- TRAF
- TRAF1
- TRAF2
- TRAF3
- TRAF4
- TRAF5
- TRAF6)
- BIN1
- SH3BP2
- LDB3
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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Cell physiology: Cell signaling / Signal transduction
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| Signaling pathways |
- GPCR
- RTK
- Notch
- JAK-STAT
- Akt/PKB
- Fas apoptosis
- Hippo
- PI3K/AKT/mTOR pathway
- Integrin receptors
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| Agents |
| Receptor ligands |
- Hormones
- Neurotransmitters/Neuropeptides/Neurohormones
- Cytokines
- Growth factors
- Signaling molecules
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| Receptors |
- Cell surface
- Intracellular
- Co-receptor
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| 2nd messenger |
- cAMP-dependent pathway
- Ca2+ signaling
- Lipid signaling
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| Assistants: |
- Signal transducing adaptor protein
- Scaffold protein
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| Transcription factors |
- General
- Transcription preinitiation complex
- TFIID
- TFIIH
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| By distance |
- Juxtacrine
- Autocrine / Paracrine
- Endocrine
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| Other concepts |
- Intracrine action
- Neurocrine signaling
- Synaptic transmission
- Chemical synapse
- Neuroendocrine signaling
- Exocrine signalling
- Mechanotransduction
- Phototransduction
- Ion channel gating
- Gap junction
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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