IGF1: Difference between revisions
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== History == | == History == | ||
The role of the pancreas and therefore insulin in diabete was first discovered by Oskar von Minkowski in Strasbourg in 1889. | The role of the pancreas and therefore insulin in diabete was first discovered by Oskar von Minkowski in Strasbourg in 1889. | ||
IGF-1 was first identified in 1957 by the team of Salmon and Daughaday. In 1976, Rinderknecht and Humbel isolated IGF-1 from human cells. The protein was further analysed in 1987 by the team of Dr Mike Davis (Imperial College of London, United Kingdom) and Pr Robin Jokin (INSERM of Toulouse). | IGF-1 was first identified in 1957 by the team of Salmon and Daughaday. In 1976, Rinderknecht and Humbel isolated IGF-1 from human cells. The protein was further analysed in 1987 by the team of Dr Mike Davis (Imperial College of London, United Kingdom) and Pr Robin Jokin (INSERM of Toulouse).<ref>Mering J. Minkowski O. “Diabetes mellitus nach Pankreasextirpation” Archiv Exp Pathol Pharmacol. 1890, 26:371–87.</ref> | ||
== Biological structures and interactions == | == Biological structures and interactions == | ||
In the pituitary gland inside the brain, '''Growth Hormone''' ('''GH''') is secreted and its release enable transcription of IGF1 in liver and depending on the nutritional state, a paracrine or autocrine activation IGF-1 occurs. IGF-1 then acts as a ligand and can interact with '''Insulin Receptor protein''' and '''Insulin-like Growth Factor Binding Protein'''. | In the pituitary gland inside the brain, '''Growth Hormone''' ('''GH''') is secreted and its release enable transcription of IGF1 in liver and depending on the nutritional state, a paracrine or autocrine activation IGF-1 occurs. IGF-1 then acts as a ligand and can interact with '''Insulin Receptor protein''' and '''Insulin-like Growth Factor Binding Protein'''. <ref>Butler, A.A., Le Roith, D., “Control of growth by the somatropic axis: Growth hormone and the insulin-like growth factors have related and independent roles.” Annu. Rev. Physiol. 2001</ref> | ||
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[[Image:IGF1.png|900 px]] | [[Image:IGF1.png|900 px]] | ||
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'''Insulin-like Growth Factor 1 Receptor''' ('''IGF-1R''') is a transmembrane protein receptor. It is composed of two α subunits and two tyrosine β subunits. Both α subunits are '''cysteine-rich region''' and therefore linked with a '''disulfide bond'''. Ligand-binding on α subunit induces activation of β subunit by autophosphorylation. It further leads to activation of the Akt and mTor pathways inside the cell. | '''Insulin-like Growth Factor 1 Receptor''' ('''IGF-1R''') is a transmembrane protein receptor. It is composed of two α subunits and two tyrosine β subunits. Both α subunits are '''cysteine-rich region''' and therefore linked with a '''disulfide bond'''. Ligand-binding on α subunit induces activation of β subunit by autophosphorylation. It further leads to activation of the Akt and mTor pathways inside the cell. | ||
[[Image:Interactions_IGF_refait.PNG | 300 px |left]] | |||
Due to their homology sequences, the three members of the '''insulin protein family''': IGF-1, IGF-2 and Insulin can interact with one another of the different receptors. Hence, Insulin binds to IGF1R following the same mechanism and activated the intracellular pathways in the same way IGF1 does. | Due to their homology sequences, the three members of the '''insulin protein family''': IGF-1, IGF-2 and Insulin can interact with one another of the different receptors. Hence, Insulin binds to IGF1R following the same mechanism and activated the intracellular pathways in the same way IGF1 does. | ||
Therefore, the various concentration of the insulin proteins regulates the cell activity in different context, for instance in excess of glucose or lack of Growth Hormone. | Therefore, the various concentration of the insulin proteins regulates the cell activity in different context, for instance in excess of glucose or lack of Growth Hormone. | ||
Recent research demonstrated that the homology between IGF-1R and the insulin receptor (IR) subunits allow them to bind and form a functionnal hybrid IR/IGF-1R receptor. | |||
<Structure load='1wqj' size='250' frame='true' align='left' caption='IGF-1/IGFBP-4 Complex' /> | |||
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IGF-1 docks IGFBP with a series of polar and non-polar interactions all along its binding site. For instance, when IGF-1 binds IGFBP-4, <scene name='75/751772/Igf-1_docking_on_igfbp/1'>VAL48 matches PHE16</scene>. Both are hydrophobic residues. This mechanism can also be applied to all interactions between proteins of the insulin protein family such as the docking of IGF-2 in IGFBP-5. | IGF-1 docks IGFBP with a series of polar and non-polar interactions all along its binding site. For instance, when IGF-1 binds IGFBP-4, <scene name='75/751772/Igf-1_docking_on_igfbp/1'>VAL48 matches PHE16</scene>. Both are hydrophobic residues. This mechanism can also be applied to all interactions between proteins of the insulin protein family such as the docking of IGF-2 in IGFBP-5. | ||
