Sandbox Reserved 1124: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 28: | Line 28: | ||
== Structure == | == Structure == | ||
Grb2 is a small protein of 217 residues with a molecular mass of about 25,206 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. The two SH3 domains bind proline-rich regions of other proteins and enable the interaction with the Sos protein (Son of Sevenless, guanine nucleotide exchange factor). Moreover it has no catalytic domain. The Grb2 protein can exist in two states : monomeric or dimeric. However, only the monomeric Grb2 conformation is able to bind SOS protein and regulate MAP kinases. In this case, the dimeric Grb2 plays the role of an inhibitor. In fact, the dimer dissociation allows the phosphorylation of Grb2 160 tyrosine and the bond of SH2 domain with phosphorylated tyrosines. To conclude, the switch between these two conformations controls the MAP kinase activity. | Grb2 is a small protein of 217 residues with a molecular mass of about 25,206 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. The two SH3 domains bind proline-rich regions of other proteins and enable the interaction with the Sos protein (Son of Sevenless, guanine nucleotide exchange factor). Moreover it has no catalytic domain. The Grb2 protein can exist in two states : monomeric or dimeric. However, only the monomeric Grb2 conformation is able to bind SOS protein and regulate MAP kinases. In this case, the dimeric Grb2 plays the role of an inhibitor. In fact, the dimer dissociation allows the phosphorylation of Grb2 160 tyrosine and the bond of SH2 domain with phosphorylated tyrosines. To conclude, the switch between these two conformations controls the MAP kinase activity..<ref name="anaïs"/> | ||
| Line 86: | Line 86: | ||
== Disease == | == Disease == | ||
Grb2 is an intermediate protein and recruits signalling molecules to form complexes. These signalling complexes cause cellular responses like cellular proliferation or invasion which can have an impact in cancer. Grb2 can also occur in many other stages of the cancer progression : it can lead to tumorigenesis.<ref>DOI:10.1517/14728222.12.8.1021</ref> Moreover, the phosphorylation of the 160 tyrosine on Grb2 has been observed in many human cancers such as prostate, colon or breast cancers and the switch between the dimeric and monomeric conformations regulates the cancer progression.<ref >PMID: 26234419</ref> | Grb2 is an intermediate protein and recruits signalling molecules to form complexes. These signalling complexes cause cellular responses like cellular proliferation or invasion which can have an impact in cancer. Grb2 can also occur in many other stages of the cancer progression : it can lead to tumorigenesis.<ref>DOI:10.1517/14728222.12.8.1021</ref> Moreover, the phosphorylation of the 160 tyrosine on Grb2 has been observed in many human cancers such as prostate, colon or breast cancers and the switch between the dimeric and monomeric conformations regulates the cancer progression.<ref name="anaïs">PMID: 26234419</ref> | ||
