Sandbox Reserved 1124: Difference between revisions
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'''Grb2 protein''' | |||
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=='''Function'''== | =='''Function'''== | ||
'''MAP kinases pathway''' | |||
In the cytosol, Grb2 is bound to the guanine nucleotide exchange factor SOS-1 via its SH3 domain. Then, this complexe is recruited to the plasmic membrane to be close the Ras protein. To help Grb2 binds the phosphorylated tyrosines of the EGFR via its two SH2 domains. The Ras protein is a small GTPase which is in an inactive state when it is bound to GDP. However, the exchange of GDP for GTP actives it allowing the bond and the activation of Raf 1, a serine/threonine protein kinase. A cascade of kinase phosphorylation is then initiated. Indeed, Raf 1 phosphorylates MEK1 or MEK 2 which in turn phosphorylate ERK1 or ERK2. Finally, these MAP kinases allow the translocation of transcription factors to the nucleus and their phosphorylation. Such as STAT 1 or Elk-1.<ref name="A"/> | In the cytosol, Grb2 is bound to the guanine nucleotide exchange factor SOS-1 via its SH3 domain. Then, this complexe is recruited to the plasmic membrane to be close the Ras protein. To help Grb2 binds the phosphorylated tyrosines of the EGFR via its two SH2 domains. The Ras protein is a small GTPase which is in an inactive state when it is bound to GDP. However, the exchange of GDP for GTP actives it allowing the bond and the activation of Raf 1, a serine/threonine protein kinase. A cascade of kinase phosphorylation is then initiated. Indeed, Raf 1 phosphorylates MEK1 or MEK 2 which in turn phosphorylate ERK1 or ERK2. Finally, these MAP kinases allow the translocation of transcription factors to the nucleus and their phosphorylation. Such as STAT 1 or Elk-1.<ref name="A"/> | ||
Moreover, the SH2 domain recognizes the C-terminal domain of FAK (Focal Adhesion Kinase) called the focal adhesion targeting region (FAT) when its tyrosine 925 on the first helix is phosphorylated. But, this tyrosine contains the pY925 motif and is not a β-turn structure. Thus, an adaptation of this tyrosine on the SH2 domain is possible. To conclude, the interaction between Grb2 and FAK leads to the activation of the Ras-MAPK pathway. | Moreover, the SH2 domain recognizes the C-terminal domain of FAK (Focal Adhesion Kinase) called the focal adhesion targeting region (FAT) when its tyrosine 925 on the first helix is phosphorylated. But, this tyrosine contains the pY925 motif and is not a β-turn structure. Thus, an adaptation of this tyrosine on the SH2 domain is possible. To conclude, the interaction between Grb2 and FAK leads to the activation of the Ras-MAPK pathway. | ||
'''PI3K/AKT pathway''' | |||
In epithelial cells, an adaptator called Gab1 binds the carboxyl terminal SH3 domain of Grb2. This causes the activation of PI3K/AKT pathway.<ref name="A"/> | In epithelial cells, an adaptator called Gab1 binds the carboxyl terminal SH3 domain of Grb2. This causes the activation of PI3K/AKT pathway.<ref name="A"/> | ||
'''T cells''' | |||
When TCR are stimulated, the membrane protein called p36-38 is phosphorylated in the T cells. Then, the phosphorylated tyrosines bind the SH2 domains of Grb2 whereas the SH3 domains are bound to Vav proteins. These interactions allow the T cell proliferation, the calcium flux in these cells and the MAP kinase activation.<ref name="A"/> | When TCR are stimulated, the membrane protein called p36-38 is phosphorylated in the T cells. Then, the phosphorylated tyrosines bind the SH2 domains of Grb2 whereas the SH3 domains are bound to Vav proteins. These interactions allow the T cell proliferation, the calcium flux in these cells and the MAP kinase activation.<ref name="A"/> | ||
== Disease == | == '''Disease''' == | ||
The phosphorylation of the 160 tyrosine on Grb2 has been observed in many human cancers such as prostate, colon or breast cancers. The switch between the dimeric and monomeric conformations regulates the cancer progression. | The phosphorylation of the 160 tyrosine on Grb2 has been observed in many human cancers such as prostate, colon or breast cancers. The switch between the dimeric and monomeric conformations regulates the cancer progression. | ||
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</StructureSection> | </StructureSection> | ||
== References == | == '''References''' == | ||
<references/> | <references/> | ||
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