التفاصيل البيبلوغرافية
| العنوان: |
The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex |
| المؤلفون: |
Luo, Ji, Field, Seth J, Lee, Jennifer Y, Engelman, Jeffrey A, Cantley, Lewis C |
| المصدر: |
Journal of Cell Biology, vol 170, iss 3 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2005 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Brain Disorders, 1.1 Normal biological development and functioning, Underpinning research, Life on Land, Animals, CHO Cells, Cricetinae, Cricetulus, Cytosol, Dimerization, Down-Regulation, Green Fluorescent Proteins, Humans, Insulin Receptor Substrate Proteins, Mice, Phosphatidylinositol 3-Kinases, Phosphoproteins, Phosphorylation, Protein Binding, Protein Subunits, Protein Transport, Receptor, IGF Type 1, Recombinant Fusion Proteins, Signal Transduction, Tyrosine, Biological Sciences, Medical and Health Sciences, Developmental Biology |
| جغرافية الموضوع: |
455 - 464 |
| الوصف: |
Phosphoinositide (PI) 3-kinase is required for most insulin and insulin-like growth factor (IGF) 1-dependent cellular responses. The p85 regulatory subunit of PI 3-kinase is required to mediate the insulin-dependent recruitment of PI 3-kinase to the plasma membrane, yet mice with reduced p85 expression have increased insulin sensitivity. To further understand the role of p85, we examined IGF-1-dependent translocation of p85alpha by using a green fluorescence protein (GFP)-tagged p85alpha (EGFP-p85alpha). In response to IGF-1, but not to PDGF signaling, EGFP-p85alpha translocates to discrete foci in the cell. These foci contain the insulin receptor substrate (IRS) 1 adaptor molecule, and their formation requires the binding of p85 to IRS-1. Surprisingly, monomeric p85 is preferentially localized to these foci compared with the p85-p110 dimer, and these foci are not sites of phosphatidylinositol-3,4,5-trisphosphate production. Ultrastructural analysis reveals that p85-IRS-1 foci are cytosolic protein complexes devoid of membrane. These results suggest a mechanism of signal down-regulation of IRS-1 that is mediated by monomeric p85 through the formation of a sequestration complex between p85 and IRS-1. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt81c5q6kg; https://escholarship.org/uc/item/81c5q6kgTest |
| الإتاحة: |
https://escholarship.org/uc/item/81c5q6kgTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.3BD1D283 |
| قاعدة البيانات: |
BASE |
