Growth factor receptor-bound protein: Difference between revisions

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**[[2aoa]], [[2aob]] – hGRB2 SH2 domain + peptide mimetic<br />
**[[2aoa]], [[2aob]] – hGRB2 SH2 domain + peptide mimetic<br />
**[[1tze]], [[1bmb]], [[1bm2]], [[1zfp]], [[1fyr]], [[1jyq]], [[1jyr]], [[2h5k]], [[3c7i]], [[3imd]], [[3imj]], [[3in7]], [[3in8]], [[3kfj]], [[3n8m]], [[3n7y]], [[3n84]], [[3mxc]], [[3mxy]], [[3ov1]], [[3ove]], [[3s8l]], [[3s8n]], [[3s8o]], [[1zfp]], [[4p9v]], [[4p9z]] – hGRB2 SH2 domain + phosphor-Tyr peptide<br />
**[[1tze]], [[1bmb]], [[1bm2]], [[1zfp]], [[1fyr]], [[1jyq]], [[1jyr]], [[2h5k]], [[3c7i]], [[3imd]], [[3imj]], [[3in7]], [[3in8]], [[3kfj]], [[3n8m]], [[3n7y]], [[3n84]], [[3mxc]], [[3mxy]], [[3ov1]], [[3ove]], [[3s8l]], [[3s8n]], [[3s8o]], [[1zfp]], [[4p9v]], [[4p9z]] – hGRB2 SH2 domain + phosphor-Tyr peptide<br />
**[[5cdw]] – hGRB2 SH2 domain (mutant) + phosphor-Tyr peptide <br />
**[[1qg1]] – hGRB2 SH2 domain + phosphor-Tyr peptide - NMR<br />
**[[1qg1]] – hGRB2 SH2 domain + phosphor-Tyr peptide - NMR<br />
**[[3wa4]] - hGRB2 SH2 domain + CD28 peptide <br />
**[[3wa4]] - hGRB2 SH2 domain + CD28 peptide <br />
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*GRB7  
*GRB7  


**[[2qms]] – hGRB7 SH2 domain <br />
**[[2qms]], [[4wwq]] – hGRB7 SH2 domain <br />
**[[4x6s]], [[5d0j]], [[5eel]], [[5eeq]] – hGRB7 SH2 domain + phosphor-Tyr peptide <br />
**[[1mw4]], [[2l4k]] – hGRB7 SH2 domain + phosphor-Tyr peptide - NMR<br />
**[[1mw4]], [[2l4k]] – hGRB7 SH2 domain + phosphor-Tyr peptide - NMR<br />
**[[3pqz]] – hGRB7 SH2 domain + cyclic peptide <br />
**[[3pqz]] – hGRB7 SH2 domain + cyclic peptide <br />

Revision as of 10:02, 5 June 2017

Function

Growth factor receptor-bound proteins (GRB) are adaptor proteins. GRBs contain SH2, Ras-associated (RA) and pleckstrin homology (PH) domains.

  • GRB2 links the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases. GRB2 contains an SH2 domain which binds tyrosine phosphorylated sequences and 2 SH3 domains which direct complex formation of proline-rich sequences. GRB2 is involved in signal transduction[1].
  • GRB7 interacts with EGFR and ephrin receptors and plays a role in itegrin signalling pathway[2].
  • GRB10 and GRB14 interact with insulin receptor and insulin-like growth factor receptors[3]. For additional details on GRB10 see Grb10 SH2 Domain.

Structural highlights

Human GRB2 residue into a turn conformation. [4].

Structure of human Grb2 SH2 domain (green) complex with phosphotyrosyl polypeptide (magenta) (PDB entry 1bmb)

Drag the structure with the mouse to rotate

3D structures of growth factor receptor-bound proteins3D structures of growth factor receptor-bound proteins

Updated on 05-June-2017

ReferencesReferences

  1. ↑ Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431-42. PMID:1322798
  2. ↑ Nadler Y, Gonzalez AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Ann Oncol. 2010 Mar;21(3):466-73. doi: 10.1093/annonc/mdp346. Epub 2009 Aug 28. PMID:19717535 doi:http://dx.doi.org/10.1093/annonc/mdp346
  3. ↑ Deng Y, Bhattacharya S, Swamy OR, Tandon R, Wang Y, Janda R, Riedel H. Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action. J Biol Chem. 2003 Oct 10;278(41):39311-22. Epub 2003 Jun 3. PMID:12783867 doi:http://dx.doi.org/10.1074/jbc.M304599200
  4. ↑ Ettmayer P, France D, Gounarides J, Jarosinski M, Martin MS, Rondeau JM, Sabio M, Topiol S, Weidmann B, Zurini M, Bair KW. Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1). J Med Chem. 1999 Mar 25;42(6):971-80. PMID:10090780 doi:10.1021/jm9811007

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Jaime Prilusky, Joel L. Sussman
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