IGF1: Difference between revisions
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<Structure load='1gzr' size='400' frame='true' align='right' caption=' | <Structure load='1gzr' size='400' frame='true' align='right' caption='IGF-1 structural basis (PDB code [[1gzr]])' scene='75/751772/Igf-1/2'/> | ||
'''Insulin-like Growth Factor''' ('''IGF-1''') is a member of the insulin protein family. '''Insulin''' is an essential endocrine protein. Indeed, it is the only hypoglycemic hormone of the human body. This protein is secreted in the beta cells of the Langerhans’ islet in the pancreas and takes part in the glycogenesis. This molecule helps the transportation of glucose into the cells, thus reducing the blood sugar rate, contrary to glucagon. | '''Insulin-like Growth Factor''' ('''IGF-1''') is a member of the insulin protein family. '''Insulin''' is an essential endocrine protein. Indeed, it is the only hypoglycemic hormone of the human body. This protein is secreted in the beta cells of the Langerhans’ islet in the pancreas and takes part in the glycogenesis. This molecule helps the transportation of glucose into the cells, thus reducing the blood sugar rate, contrary to glucagon. | ||
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IGF-1 is a peptidic hormone of 69 amino acids which is secreted by the liver. | IGF-1 is a peptidic hormone of 69 amino acids which is secreted by the liver. | ||
This protein deals with a large scale of regulations, from growth to nutrition and it is even implied in stress response, breeding and longevity.<ref>Patrick Jouandin. Rôle de la voie de signalisation Insuline dans le couplage des informations nutritionnelles et développementales au cours de l'ovogenèse chez la drosophile. Sciences agricoles.Université Nice Sophia Antipolis, 2013. Français.<NNT : 2013NICE4102>.<tel-00932409></ref>. | This protein deals with a large scale of regulations, from growth to nutrition and it is even implied in stress response, breeding and longevity.<ref>Patrick Jouandin. Rôle de la voie de signalisation Insuline dans le couplage des informations nutritionnelles et développementales au cours de l'ovogenèse chez la drosophile. Sciences agricoles.Université Nice Sophia Antipolis, 2013. Français.<NNT : 2013NICE4102>.<tel-00932409></ref>. | ||
It is the main actor in primary growth cell control. | It is the main actor in primary growth cell control. | ||
See also: | |||
*[[Insulin-like growth factor]] | |||
*[[Insulin-like growth factor receptor]] | |||
== 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).<ref>Mering J. Minkowski O. “Diabetes mellitus nach Pankreasextirpation” Archiv Exp Pathol Pharmacol. 1890, 26:371–87.</ref> | 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 == | ||
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<Structure load='4xss' size='250' frame='true' align='right' caption='IGF-1/IGF-1R Complex' /> | <Structure load='4xss' size='250' frame='true' align='right' caption='IGF-1/IGF-1R Complex' scene='75/751772/Igf1r/1'/> | ||
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=== Stimulating interaction : IGF-1 - IGF-1R === | === Stimulating interaction : IGF-1 - IGF-1R === | ||
'''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 '' | '''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 <scene name='75/751772/Igf1r/2'>cystein-rich region</scene> 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. <ref>http://www.exobiologie.info/diabete/10%20recepteur.pdf, 27/01/2016</ref> | ||
[[Image:Interactions_IGF_refait.PNG | 300 px |left]] | [[Image:Interactions_IGF_refait.PNG | 300 px |left]] | ||
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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. | 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. The exact residues interacting with one another are not known accuraretly but the docking mechanism is the same as for IGFBP. | ||
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'''IGF binding proteins''' ('''IGFBPs''') weight 24 to 45 kDa. All six IGFBPs share 50% homology with each other and have binding affinities at the same order of magnitude for IGF-1 and IGF-2 but have greater affinities then IGF1 for its receptor. Once IGF1 is bound to Insulin-like Growth Binding Protein (IGFBP), IGF-1 cannot be linked to IGF1R any longer. Therefore, increases in serum levels of this IGFBP result in a decrease of IGF1 activity thus inhibiting the cellular pathways. | '''IGF binding proteins''' ('''IGFBPs''') weight 24 to 45 kDa. All six IGFBPs share 50% homology with each other and have binding affinities at the same order of magnitude for IGF-1 and IGF-2 but have greater affinities then IGF1 for its receptor. Once IGF1 is bound to Insulin-like Growth Binding Protein (IGFBP), IGF-1 cannot be linked to IGF1R any longer. Therefore, increases in serum levels of this IGFBP result in a decrease of IGF1 activity thus inhibiting the cellular pathways. | ||
The IGFBPs help to lengthen the half-life of circulating IGFs in all tissues. That is why approximately 98% of IGF-1 exists as complexed form with one of the six different IGFBP. '''IGFBP-3''', the most abundant protein, accounts for 80% of all IGF binding. Inside the liver, this mechanism is responsible for positive feedback, more precisely it allows growth hormone to continuously act upon the liver to produce more IGF-1. | The IGFBPs help to lengthen the half-life of circulating IGFs in all tissues. That is why approximately 98% of IGF-1 exists as complexed form with one of the six different IGFBP. '''IGFBP-3''', the most abundant protein, accounts for 80% of all IGF binding. Inside the liver, this mechanism is responsible for positive feedback, more precisely it allows growth hormone to continuously act upon the liver to produce more IGF-1.<ref>W Kalus, M Zweckstetter, C Renner, Y Sanchez, J Georgescu, M Grol, D Demuth, R Schumacher, C Dony, K Lang, and T A Holak, “Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions”, The EMBO Journal Vol.17 No.22 pp.6558–6572, 1998</ref> | ||
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. | ||