Grb10 SH2 Domain: Difference between revisions
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<StructureSection load='1NRV' size='350' side='right' caption='Crystal Structure of the SH2 Domain of Grb10 (PDB entry [[ | <StructureSection load='1NRV' size='350' side='right' caption='Crystal Structure of the SH2 Domain of Grb10 (PDB entry [[1nrv]])' scene=''> | ||
==Introduction== | ==Introduction== | ||
Grb10 (Growth factor Receptor-Binding protein) is the member of a family of adapter proteins (Grb7 and Grb14) that interacts with tyrosine kinases. <ref name=Guan>PMID: 12551896 </ref> This protein acts as a growth suppressor by competitively binding to insulin receptors and IGF1R [[Insulin-like growth factor 1 receptor]] which prevents other hormones to bind and facilitate chemical reactions within the cell. It has also been found to interact with E3 Ubiquitin Ligase NEDD4 which promotes the degradation of IGF1R. New developments in the research of Grb10 have shown that by inhibiting the expression of this gene, mice express a phenotype that has an increase in body mass, improved glucose homeostasis, improved insulin sensitivity and reduced adiposity. Grb10 knockout mice have a 30% increase in muscle mass, which has designated it to be called the 'Hulk' protein. | '''Grb10 (Growth factor Receptor-Binding protein)''' is the member of a family of adapter proteins (Grb7 and Grb14) that interacts with tyrosine kinases. <ref name=Guan>PMID: 12551896 </ref> This protein acts as a growth suppressor by competitively binding to [[insulin receptors]] and IGF1R ([[Insulin-like growth factor 1 receptor]]) which prevents other hormones to bind and facilitate chemical reactions within the cell. It has also been found to interact with E3 Ubiquitin Ligase NEDD4 which promotes the degradation of IGF1R. New developments in the research of Grb10 have shown that by inhibiting the expression of this gene, mice express a phenotype that has an increase in body mass, improved glucose homeostasis, improved insulin sensitivity and reduced adiposity. Grb10 knockout mice have a 30% increase in muscle mass, which has designated it to be called the 'Hulk' protein. | ||
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==Interaction Between Grb10 and E3 Ubiquitin Ligase NEDD4== | ==Interaction Between Grb10 and E3 Ubiquitin Ligase NEDD4== | ||
<Structure load='3M7F' size='350' frame='true' align='left' caption='Crystal structure of the Nedd4 C2/Grb10 SH2 complex PDB entry [[ | <Structure load='3M7F' size='350' frame='true' align='left' caption='Crystal structure of the Nedd4 C2/Grb10 SH2 complex PDB entry [[3m7f]])' scene='Insert optional scene name here' /> | ||
Grb10 has now been shown to not only inhibit insulin receptors and IGF1R kinase activity, but also interacts via its SH2 domain with the C2 domain of E3 ubiquitin ligase NEDD4 facilitating ubiquitation of IGF1R <ref>PMID: 20980250</ref>. It is hypothesized that the Grb10 SH2 interaction with the E3 domain of NEDD4 may allow NEDD4 to come in close proximity to IGF1R promoting degradation.<ref>PMID: 20980250</ref> | Grb10 has now been shown to not only inhibit insulin receptors and IGF1R kinase activity, but also interacts via its SH2 domain with the C2 domain of E3 ubiquitin ligase NEDD4 facilitating ubiquitation of IGF1R <ref>PMID: 20980250</ref>. It is hypothesized that the Grb10 SH2 interaction with the E3 domain of NEDD4 may allow NEDD4 to come in close proximity to IGF1R promoting degradation.<ref>PMID: 20980250</ref> | ||
