scholarly journals Insulin and insulin-like growth factor 1 stimulate the phosphorylation on tyrosine of a 160 kDa cytosolic protein in 3T3-L1 adipocytes

1988 ◽  
Vol 252 (1) ◽  
pp. 7-15 ◽  
Author(s):  
D H Madoff ◽  
T M Martensen ◽  
M D Lane
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Beta Subunit ◽  
Insulin Like Growth Factor ◽  
Insulin Receptor Tyrosine Kinase ◽  
Cytosolic Protein ◽  
20 Nm ◽  
Quantitative Immunoblotting ◽  
Receptor Beta

Insulin and IGF-1 (insulin-like growth factor 1) rapidly stimulate the phosphorylation on tyrosine of a 160 kDa cytosolic protein (pp160) in intact 3T3-L1 adipocytes. Half-maximal phosphorylation of pp160 is attained with either 4 nM-insulin or 20 nM-IGF-1. A semi-quantitative immunoblotting procedure using anti-phosphotyrosine antibody revealed that the insulin-stimulated 3T3-L1 adipocyte possesses approx. 3 × 10(5) and 0.6 × 10(5) phosphotyrosyl sites, respectively, in pp160 and insulin receptor beta-subunit. Removal of insulin from stimulated cells results in the rapid (within 15 min) loss of phosphate groups from tyrosyl residues in both pp160 and receptor beta-subunit. Whereas pp160 remains maximally phosphorylated on tyrosine for up to 60 min in the presence of 100 nM-insulin, IGF-1 at the same concentration induces only a transient response that is maximally 50% of that observed with insulin. pp160 is not phosphorylated on tyrosine in response to platelet-derived growth factor or epidermal growth factor. Although pp160 appears to be a soluble cytoplasmic protein, in the presence of 1 mM-ZnCl2 it becomes membrane-associated. In view of its apparent cytoplasmic localization and its inability to bind to either wheat-germ agglutinin or concanavalin A, pp160 does not appear to be a typical glycoprotein growth-factor receptor. Our results suggest that pp160 may be a physiologically important cellular substrate of the insulin-receptor tyrosine kinase in the intact 3T3-L1 adipocyte.

scholarly journals Secretion of Annexin II via Activation of Insulin Receptor and Insulin-like Growth Factor Receptor

2002 ◽  
Vol 278 (6) ◽  
pp. 4205-4215 ◽  
Author(s):  
Wei-Qin Zhao ◽  
Gina H. Chen ◽  
Hui Chen ◽  
Alessia Pascale ◽  
Lakshmi Ravindranath ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Annexin Ii ◽  
Insulin Like Growth Factor

scholarly journals Determination of Alkali-Sensing Parts of the Insulin Receptor-Related Receptor Using the Bioinformatic Approach

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 80-86 ◽  
Author(s):  
I. E. Deyev ◽  
N. V. Popova ◽  
A. G. Petrenko
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Ph Sensitive ◽  
Effective Concentration ◽  
The Body ◽  
Insulin Like Growth Factor ◽  
Extracellular Region ◽  
Half Maximal Effective Concentration ◽  
Receptor Family

IRR (insulin receptor-related receptor) is a receptor tyrosine kinase belonging to the insulin receptor family, which also includes insulin receptor and IGF-IR receptor. We have previously shown that IRR is activated by extracellular fluid with pH 7.9 and regulates excess alkali excretion in the body. We performed a bioinformatic analysis of the pH-sensitive potential of all three members of the insulin receptor family of various animal species (from frog to man) and their chimeras with swapping of different domains in the extracellular region. An analysis using the AcalPred program showed that insulin receptor family proteins are divided into two classes: one class with the optimal working pH in the acidic medium (virtually all insulin receptor and insulin-like growth factor receptor orthologs, except for the IGF-IR ortholog from Xenopus laevis) and the second class with the optimal working pH in the alkaline medium (all IRR orthologs). The program had predicted that the most noticeable effect on the pH-sensitive property of IRR would be caused by the replacement of the L1 and C domains in its extracellular region, as well as the replacement of the second and third fibronectin repeats. It had also been assumed that replacement of the L2 domain would have the least significant effect on the alkaline sensitivity of IRR. To test the in silico predictions, we obtained three constructs with swapping of the L1C domains, the third L2 domain, and all three domains L1CL2 of IRR with similar domains of the insulin-like growth factor receptor. We found that replacement of the L1C and L1CL2 domains reduces the receptors ability to be activated with alkaline pH, thus increasing the half-maximal effective concentration by about 100%. Replacement of the L2 domain increased the half-maximal effective concentration by 40%. Thus, our results indicate the high predictive potential of the AcalPred algorithm, not only for the pH-sensitive enzymes, but also for pH-sensitive receptors.

Upregulation of the Insulin Receptor and Type I Insulin-Like Growth Factor Receptor Are Early Events in Hepatocarcinogenesis

2011 ◽  
Vol 39 (3) ◽  
pp. 524-543 ◽  
Author(s):  
Eiman Aleem ◽  
Dirk Nehrbass ◽  
Fritz Klimek ◽  
Doris Mayer ◽  
Peter Bannasch
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Growth Factor Receptor ◽  
Type I ◽  
Insulin Like Growth Factor
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