Sandbox Reserved 1124: Difference between revisions

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== DNA/RNA ==

The gene which codes the Grb2 protein is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2. In fact, it is a deletion in the amino-terminal part of the SH2 domain. Therefore, the function is modified because this domain cannot bind the phosphorylated tyrosine.

The gene which codes the Grb2 protein is located on the seventeen chromosome. It is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2. In fact, it is a deletion in the amino-terminal part of the SH2 domain. Therefore, the function is modified because this domain cannot bind the phosphorylated tyrosine.

== Structure ==

Line 40:

=== 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. ~~This~~ 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.

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.

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.

=== 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.

</StructureSection>

== References ==

Sandbox Reserved 1124: Difference between revisions

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@@ Line 14: / Line 14: @@
 == DNA/RNA ==
-The gene which codes the Grb2 protein is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2. In fact, it is a deletion in the amino-terminal part of the SH2 domain. Therefore, the function is modified because this domain cannot bind the phosphorylated tyrosine.
+The gene which codes the Grb2 protein is located on the seventeen chromosome. It is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2. In fact, it is a deletion in the amino-terminal part of the SH2 domain. Therefore, the function is modified because this domain cannot bind the phosphorylated tyrosine.
 == Structure ==
@@ Line 40: / Line 40: @@
 === 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. This 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.
+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.
+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.
+=== 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.
 </StructureSection>
 == References ==