Journal article
Activation of the Insulin-like Growth Factor Type 1 Receptor by Deletion of Amino Acids 870–905
Experimental cell research, v 243(2), pp 326-333
15 Sep 1998
PMID: 9743592
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have created a deletion mutant of the insulin-like growth factor type 1 receptor (IGF-1 R) which lacks the 36 amino acids (aa) immediately N-terminal to the transmembrane domain (Δ870–905 IGF-1 R). This region has been reported to have a negative effect on the transforming potential of an avian sarcoma virus gag-IGF-1 R fusion protein. We have sought to determine whether this region plays a similar role in the intact IGF-1 R. Analysis of the tyrosine kinase activity of the Δ870–905 IGF-1 R shows that the mutant receptor is autophosphorylated without IGF-1 stimulation, indicating that the tyrosine kinase domain is constitutively active. In addition, processing of the receptor is decreased, resulting in accumulation of a high molecular weight proreceptor containing both α and β-subunits. A well-characterized substrate of the IGF-1 R, IRS-1, is constitutively phosphorylated by the Δ870–905 IGF-1 R and phosphoinositide (PI) 3-kinase activity, which is normally activated by the phosphorylation of IRS-1 following IGF-1 stimulation, is increased even in the absence of IGF-1. A second intracellular signal pathway normally activated by IGF-1, the MAP kinase pathway, showed no increase in activity in the absence of IGF-1. The Δ870–905 IGF-1 R promoted cell proliferation only in the presence of IGF-1. We conclude that this deletion increases the basal activity of the IGF-1 receptor tyrosine kinase and activates PI 3-kinase, but is unable to stimulate MAP kinase in the absence of ligand. These results confirm those seen in the gag-IGF-1 R fusion protein and indicate that aa 870–905 exert a negative effect on the tyrosine kinase domain of the β-subunit of the IGF-1 R.
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Details
- Title
- Activation of the Insulin-like Growth Factor Type 1 Receptor by Deletion of Amino Acids 870–905
- Creators
- Shu Li - Allegheny University of the Health SciencesHong Zhang - Allegheny CollegeHenry Hoff - Allegheny CollegeChristian Sell - Allegheny CollegeHua Zhang - Electrical and Computer Engineering
- Publication Details
- Experimental cell research, v 243(2), pp 326-333
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Electrical and Computer Engineering
- Web of Science ID
- WOS:000076241700012
- Scopus ID
- 2-s2.0-0032531140
- Other Identifier
- 991019168300404721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell Biology
- Oncology