PMID:11884589

Citation	Buckley, DA, Cheng, A, Kiely, PA, Tremblay, ML and O'Connor, R (2002) Regulation of insulin-like growth factor type I (IGF-I) receptor kinase activity by protein tyrosine phosphatase 1B (PTP-1B) and enhanced IGF-I-mediated suppression of apoptosis and motility in PTP-1B-deficient fibroblasts. Mol. Cell. Biol. 22:1998-2010
Abstract	The insulin-like growth factor type I (IGF-I) receptor (IGF-IR), activated by its ligands IGF-I and IGF-II, can initiate several signal transduction pathways that mediate suppression of apoptosis, proliferation, differentiation, and transformation. Here we investigated the regulation of IGF-IR activation and function by protein tyrosine phosphatase 1B (PTP-1B). Coexpression of PTP-1B with a beta-chain construct of the IGF-IR (betaWT) inhibited IGF-IR kinase activity in fission yeast Schizosaccharomyces pombe, in COS cells, and in IGF-IR-deficient fibroblasts. In both spontaneously immortalized and simian virus 40 T antigen-transformed embryonic fibroblast cell lines derived from PTP-1B knockout mice, IGF-I induced higher levels of IGF-IR autophosphorylation and kinase activity than were induced in PTP-1B-expressing control cells. PTP-1B-deficient cells exhibited enhanced IGF-I-mediated protection from apoptosis in response to serum withdrawal or etoposide killing, as well as enhanced plating efficiency and IGF-I-mediated motility. Reexpression of PTP-1B in spontaneously immortalized fibroblasts resulted in decreased IGF-IR and AKT activation, as well as decreased protection from apoptosis and decreased motility. These findings demonstrate that PTP-1B can regulate IGF-IR kinase activity and function and that loss of PTP-1B can enhance IGF-I-mediated cell survival, growth, and motility in transformed cells.
Links	PubMed PMC133665
Keywords	Animals; Apoptosis/drug effects; Blotting, Western; Cell Line; Cell Movement/drug effects; Cell Survival; Cells, Cultured; Cloning, Molecular; Culture Media, Serum-Free/pharmacology; Enzyme Activation/drug effects; Fibroblasts/cytology; Fibroblasts/drug effects; Fibroblasts/enzymology; Gene Deletion; Insulin-Like Growth Factor I/pharmacology; Mice; Mitogen-Activated Protein Kinases/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Protein Subunits; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases/genetics; Protein Tyrosine Phosphatases/metabolism; Receptor, IGF Type 1/genetics; Receptor, IGF Type 1/metabolism; Schizosaccharomyces/cytology; Schizosaccharomyces/drug effects; Schizosaccharomyces/enzymology; Time Factors; Wound Healing
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IGF1R	enables	GO:0004713: protein tyrosine kinase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:IGF1R		GO:0004713: protein tyrosine kinase activity	ECO:0000315:		F		Fig1B	complete CACAO 3654

References

See Help:References for how to manage references in GONUTS.