Effects of general receptor for phosphoinositides 1 on insulin and insulin-like growth factor I-induced cytoskeletal rearrangement, glucose transporter-4 translocation, and deoxyribonucleic acid synthesis

Détails

ID Serval
serval:BIB_75916CF5068C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effects of general receptor for phosphoinositides 1 on insulin and insulin-like growth factor I-induced cytoskeletal rearrangement, glucose transporter-4 translocation, and deoxyribonucleic acid synthesis
Périodique
Endocrinology
Auteur⸱e⸱s
Clodi  M., Vollenweider  P., Klarlund  J., Nakashima  N., Martin  S., Czech  M. P., Olefsky  J. M.
ISSN
0013-7227 (Print)
Statut éditorial
Publié
Date de publication
12/1998
Volume
139
Numéro
12
Pages
4984-90
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Dec
Résumé
We investigated the effects of general receptor for phosphoinositides-1 (GRP1), a recently cloned protein that binds 3,4,5-phosphatidylinositol [PtdIns(3,4,5)P3] with high affinity, but not PtdIns(3,4)P2 nor PtdIns(3)P, on insulin and insulin-like growth factor I (IGF-I)-induced cytoskeletal rearrangement, glucose transporter-4 (GLUT4) translocation, and DNA synthesis. GRP1 consists of an NH2-terminally located coiled coil domain followed by a Sec7 domain and a COOH-terminal pleckstrin homology (PH) domain that is required for PtdIns binding. We used microinjection of glutathione-S-transferase fusion proteins containing residues 239-399 (PH domain), residues 52-260 (Sec7 domain), residues 5-71 (N-terminal domain), full-length GRP1, and an antibody (AB) raised against full-length GRP1 coupled with immunofluorescent detection of actin filament rearrangement, GLUT4 translocation, and 3'-bromo-5'-deoxyuridine incorporation. Microinjection of these constructs and the AB had no effect on insulin-induced GLUT4 translocation or DNA synthesis. However, microinjection of the GRP1-PH and the GRP1-Sec7 domain as well as the alpha-GRP1-AB significantly inhibited insulin- and IGF-I-stimulated actin rearrangement in an insulin receptor-overexpressing cell line (HIRcB) compared with that in control experiments. Coinjection of GRP1-Sec7 along with constitutively active Rac (Q67L) did not inhibit Rac-induced actin rearrangement. Furthermore, GRP1 is not able to bind and act as a nucleotide exchange factor for the small GTP-binding proteins of the Rho family. As GRP1 acts as a guanine nucleotide exchange factor for ARF6 proteins, we propose a signaling pathway distinct from the small GTP-binding protein Rac, connecting PtdIns(3,4,5)P3 via GRP1 to ARF6, leading to insulin- and IGF-I-induced actin rearrangement.
Mots-clé
3T3 Cells Adipocytes/metabolism Animals Biological Transport/drug effects Cell Line Cytoskeleton/*drug effects/ultrastructure DNA/*biosynthesis Fibroblasts/metabolism GTP-Binding Proteins/physiology Glucose Transporter Type 4 Insulin/*pharmacology Insulin-Like Growth Factor I/*pharmacology Mice Microinjections Monosaccharide Transport Proteins/*metabolism *Muscle Proteins Rats Receptors, Cytoplasmic and Nuclear/*physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 14:06
Dernière modification de la notice
20/08/2019 14:33
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