INSR Membrane Protein Introduction

Introduction of INSR

INSR encoded by INSR gene is a member of the receptor tyrosine kinase family. The encoded protein has 1382 acid amino acids with a molecular weight of about 300 kDa. INSR is a heterotetramer which consists of two α subunits and two β subunits, bound together by disulfide bonds. The α subunits are extracellular and contain the insulin-binding domain. The β subunits are composed of an extracellular domain, a transcellular domain, and an intracellular domain with insulin-stimulated kinase activity.

Function of INSR Membrane Protein

INSR is found on the surface of many types of cells such as liver, muscle, and fat. Insulin binds to INSR and thus leads to tyrosine autophosphorylation of the β subunit. Then, it phosphorylates other substrates such as insulin receptor substrates (IRS1, 2, 3, 4). These phosphorylated substrates subsequently activate two main signaling cascades including the PI3K-AKT/PKB pathway as well as the Ras-MAPK pathway and involve many biological responses. The PI3K-AKT/PKB pathway is associated with the actions of insulin and regulates glucose uptake and release. For example, the activated PIP3-dependent serine/threonine kinases (PDPK1 and AKT/PKB) participate in the translocation of glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to promote glucose transport. Moreover, activated AKT/PKB can suppress the apoptotic effect of insulin. Besides, the insulin-mediated Ras-MAPK pathway is involved in the regulation of cell growth and differentiation. Most studies have shown that insulin signaling exerts an important role in energy homeostasis, cognitive functioning, reproductive development, and sympathetic nervous system activity in the central nervous system. In addition, insulin signaling is also associated with many pathological processes, such as cardiovascular diseases, obesity, hypoglycemia, and diabetes mellitus.

Fig.1 Signal transduction via the insulin receptor and its downstream signaling proteins. (Martyn, 2008)

Application of INSR Membrane Protein in Literature

1. Brierley G.V., et al. Evaluation of anti-insulin receptor antibodies as potential novel therapies for human insulin receptoropathy using cell culture models. Diabetologia. 2018, 61(7): 1662-1675. PubMed ID: 29700562
   
   

   The study shows that anti-INSR monoclonal antibodies involve the activation of selected naturally occurring mutant human INSRs. This may provide a novel therapy for insulin resistance induced by recessive mutations.

2. Takasawa K., et al. Clinical characteristics of adolescent cases with type A insulin resistance syndrome caused by heterozygous mutations in the β-subunit of INSR. Journal of Diabetes. 2018. PubMed ID: 29877041
   
   

   The study finds four heterozygous missense mutations of the β-subunit of INSR in Type A insulin resistance (IR). However, there are no significant differences in clinical phenotypes between Type A IR induced by INSR mutations and Type A IR induced by other factors.

3. Juárez-Vázquez C.I., et al. Insulin glargine affects the expression of Igf-1r, Insr, and Igf-1 genes in colon and liver of diabetic rats. Iranian Journal of Basic Medical Science. 2018, 21(5): 489-494. PubMed ID: 29922429
   
   

   The study indicates that the overexpression of the Insr and Igf-1r genes are detected in liver tissue of rats which are treated with glargine compared to control group. This suggests glargine can promote an excess of insulin and IGF-1 receptors in STZ-induced diabetic rats.

4. Sun J., et al. Up-regulation of INSR/IGF1R by C-myc promotes TSCC tumorigenesis and metastasis through the NF-κB pathway. Biochimica et Biophysica Acta. 2018, 1864(5 Pt A): 1873-1882. PubMed ID: 29518496
   
   

   The study indicates that the increasing levels of INSR/IGF1R by C-myc facilitate tumorigenesis and metastasis of tongue squamous cell carcinoma via the NF-κB pathway.

INSR Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-INSR antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

As a forward-looking custom service provider in the field of membrane protein, Creative Biolabs has won good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.

Reference

1. Martyn J A, et al. (2008). Obesity-induced insulin resistance and hyperglycemia: etiologic factors and molecular mechanisms. Anesthesiology. 109(1): 137-48.

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