| Structural highlights
6vk2 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 1bmb, 1bm2, 1fhs, 1jyq, 1jyr, 1jyu, 1qg1, 1tze, 1zfp, 2aoa, 2h46, 2h5k, 2how, 3c7i, 3imd, 3imj, 3in7, 3kfj, 3mxc, 3n7y, 3n84, 3n8m, 3ov1, 3s8l, 3wa4 |
| Gene: | GRB2, ASH (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GRB2_HUMAN] Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.[1] [2] [3] Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.[4] [5] [6]
Publication Abstract from PubMed
Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein composed of three domains, an N-terminal SH3 (nSH3), SH2 and a C-terminal SH3 (cSH3) domains. This multi-domain protein has been reported to be a key factor in many signaling pathways related to controlling cell survival, differentiation, and growth. The Grb2-SH2 domain has been a focus for the study of the interaction with peptides and small molecules to act as inhibitors in uncontrolled cell growth, and consequently inhibit tumor proliferation. Here we describe the almost complete assignment of the free SH2 domain at pH 7. This work prepares the ground for further structural studies, backbone dynamics, mapping of interactions and drug screening and development. TalosN secondary structure prediction showed great similarity with the available structures in the PDB.
NMR assignment of free (1)H, (15)N and (13)C-Grb2-SH2 domain.,Sanches K, Caruso IP, Almeida FCL, Melo FA Biomol NMR Assign. 2019 Oct;13(2):295-298. doi: 10.1007/s12104-019-09894-x. Epub , 2019 Apr 26. PMID:31028611[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocque B. Cloning of a Grb2 isoform with apoptotic properties. Science. 1994 May 13;264(5161):971-4. PMID:8178156
- ↑ Pao-Chun L, Chan PM, Chan W, Manser E. Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J Biol Chem. 2009 Dec 11;284(50):34954-63. doi: 10.1074/jbc.M109.072660. Epub, 2009 Oct 8. PMID:19815557 doi:10.1074/jbc.M109.072660
- ↑ 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
- ↑ Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocque B. Cloning of a Grb2 isoform with apoptotic properties. Science. 1994 May 13;264(5161):971-4. PMID:8178156
- ↑ Pao-Chun L, Chan PM, Chan W, Manser E. Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J Biol Chem. 2009 Dec 11;284(50):34954-63. doi: 10.1074/jbc.M109.072660. Epub, 2009 Oct 8. PMID:19815557 doi:10.1074/jbc.M109.072660
- ↑ Sanches K, Caruso IP, Almeida FCL, Melo FA. NMR assignment of free (1)H, (15)N and (13)C-Grb2-SH2 domain. Biomol NMR Assign. 2019 Oct;13(2):295-298. doi: 10.1007/s12104-019-09894-x. Epub , 2019 Apr 26. PMID:31028611 doi:http://dx.doi.org/10.1007/s12104-019-09894-x
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