Structural Biology of Insulin and IGF‐1 Receptors

Meyts, Pierre De; Palsgaard, Jane; Sajid, Waseem; Theede, Anne-Mette; Aladdin, Hassan

doi:10.1002/0470869976.ch10

Cited by 44 publications

(27 citation statements)

References 7 publications

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“…The insulin receptor is a member of the superfamily of receptor tyrosine kinases. It is a dimer composed of two extracellular ␣ subunits and two transmembrane ␤ domains (De Meyts et al, 2004), in which the ␣ subunit contains the ligand binding domain and the ␤ subunit contains the tyrosine kinase sites. Binding of insulin to the insulin receptor activates signaling cascades that involve tyrosine kinases and PI3 kinases.…”

Section: Insulin Enhances Glycine Receptor Function 1281mentioning

confidence: 99%

Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors

Caraiscos

Bonin²,

Newell³

et al. 2007

Mol Pharmacol

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The mechanisms by which insulin modulates neuronal plasticity and pain processes remain poorly understood. Here we report that insulin rapidly increases the function of glycine receptors in murine spinal neurons and recombinant human glycine receptors expressed in human embryonic kidney cells. Whole-cell patch-clamp recordings showed that insulin reversibly enhanced current evoked by exogenous glycine and increased the amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents recorded in cultured spinal neurons. Insulin (1 M) also shifted the glycine concentration-response plot to the left and reduced the glycine EC 50 value from 52 to 31 M. Currents evoked by a submaximal concentration of glycine were increased to approximately 140% of control. The glycine receptor ␣ subunit was sufficient for the enhancement by insulin because currents from recombinant homomeric ␣ 1 receptors and heteromeric ␣ 1 ␤ receptors were both increased. Insulin acted at the insulin receptor via pathways dependent on tyrosine kinase and phosphatidylinositol 3 kinase because the insulin effect was eliminated by the insulin receptor antagonist, hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol 3 kinase antagonist wortmannin. Together, these results show that insulin has a novel regulatory action on the potency of glycine for ionotropic glycine receptors.

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Section: Insulin Enhances Glycine Receptor Function 1281mentioning

confidence: 99%

Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors

Caraiscos

Bonin²,

Newell³

et al. 2007

Mol Pharmacol

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“…This tyrosine kinase receptor has been implicated in several metabolic, neoplastic, and immunological diseases (2)(3)(4). IGF-1R and associated IGF-1-binding proteins constitute a cell surface signaling complex (5). An IGF-1 binding domain resides in the extracellular domain of IGF-1R␣, whereas three tyrosine residues represent autophosphorylation sites, namely Tyr 1131 , Tyr 1135 , and Tyr 1136 , within the activation loop of the IGF-1R␤ catalytic domain (6).…”

mentioning

confidence: 99%

“…Phosphorylation at all three is required for optimal receptor activation. This culminates in the recruitment of multiple docking proteins and the generation of intracellular signaling (5).…”

mentioning

confidence: 99%

Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves’ Disease May Carry Functional Consequences for Disease Pathogenesis

Douglas

Gianoukakis

Kamat

et al. 2007

The Journal of Immunology

131

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Graves’ disease (GD), an autoimmune process involving thyroid and orbital tissue, is associated with lymphocyte abnormalities including expansion of memory T cells. Insulin-like growth factor receptor-1 (IGF-1R)-bearing fibroblasts overpopulate connective tissues in GD. IGF-1R on fibroblasts, when ligated with IgGs from these patients, results in the expression of the T cell chemoattractants, IL-16 and RANTES. We now report that a disproportionately large fraction of peripheral blood T cells express IGF-1R (CD3+IGF-R+). CD3+IGF-1R+ T cells comprise 48 ± 4% (mean ± SE; n = 33) in patients with GD compared with 15 ± 3% (n = 21; p < 10−8) in controls. This increased population of IGF-1R+ T cells results, at least in part, from an expansion of CD45RO+ T cells expressing the receptor. In contrast, the fraction of CD45RA+IGF-1R+ T cells is similar in GD and controls. T cells harvested from affected orbital tissues in GD reflect similar differences in the proportion of IGF-1R+CD3+ and IGF-1R+CD4+CD3+ cells as those found in the peripheral circulation. GD-derived peripheral T cells express durable, constitutive IGF-1R expression in culture and receptor levels are further up-regulated following CD3 complex activation. IGF-1 enhanced GD-derived T cell incorporation of BrdU (p < 0.02) and inhibited Fas-mediated apoptosis (p < 0.02). These findings suggest a potential role for IGF-1R displayed by lymphocytes in supporting the expansion of memory T cells in GD.

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“…The most abundant IGFBP in bone is IGFBP5 [12,13]. IGFs are also potent mitogenic polypeptides with important regulatory roles in cellular processes such as mitosis, cell migration, and apoptosis, which are critical for embryonic development [14,15].…”

Section: The Role Of Igfsmentioning

confidence: 99%

PAPP-A2 nowy regulator procesu wzrastania

Banaszak-Ziemska

Niedziela

2017

Endokrynologia Polska

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Short stature is the main problem that paediatric endocrinologists have to grapple with. Endocrine disorders account for only 5% of patients with short stature, but this is still one of the most common causes of reports to the endocrine clinic and hospitalisation in the endocrine department. A properly functioning growth hormone/insulin-like growth factor 1 (GH/IGF1) axis is one of the most important factors in proper growth. A lot of genetic defects in this axis lead to syndromes marked by impaired growth, like Laron syndrome, mutations in the STAT5B, insulin-like growth factor 1 (IGF1), and insulin-like growth factor 1 receptor (IGF1R) and mutations in the acid labile subunit (ALS). Two proteases important for the proper functioning of the GH/IGF1 axis: pregnancy-associated plasma protein-A (PAPP-A) and pregnancy-associated plasma protein-A2 (PAPP-A2), have been described. The first description of the new syndrome of growth failure associated with mutation in the PAPP-A2 gene was given by Andrew Dauber et al. This review evaluates the current data concerning PAPP-A2 function, and particularly the effect of PAPP-A2 mutation on growth. (Endokrynol Pol 2017; 68 (6): 682-687)

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Structural Biology of Insulin and IGF‐1 Receptors

Cited by 44 publications

References 7 publications

Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors

Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors

Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves’ Disease May Carry Functional Consequences for Disease Pathogenesis

PAPP-A2 nowy regulator procesu wzrastania

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