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IRS-4 mediated mitogenic signalling by insulin and growth hormone in LB cells, a murine T-cell lymphoma devoid of IGF-I receptors.
- Source :
-
Cellular signalling [Cell Signal] 2003 Apr; Vol. 15 (4), pp. 385-94. - Publication Year :
- 2003
-
Abstract
- Insulin and growth hormone (GH) induce mitogenic and metabolic signals in cells, GH either directly or indirectly via IGF-I production. We have studied a spontaneous murine T-cell lymphoma (LB cells) devoid of IGF-1 receptors in which proliferation is maintained by insulin [Int. J. Cancer 50 (1992) 80], and show that GH is more potent than insulin, with both GH and insulin dose-response curves for thymidine incorporation being bell-shaped. Binding showed somatogenic rather than lactogenic GH receptors. Insulin stimulated phosphorylation of the insulin receptor and of a 160-kDa protein, identified as the IRS-4 protein. This phosphorylated IRS-4 associated with PI3-kinase, which was activated along with the downstream p70(S6) kinase, whereas the Ras-MAPK pathway was not. Using selective inhibitors, the PI3-kinase, but not p70(S6) kinase or MEK, was found to be involved in insulin-stimulated DNA synthesis. GH induced tyrosine phosphorylation of IRS-4 and nuclear translocation of STAT5. The LB cells constitute a new model for studying GH and insulin signalling without interference of IGF-1 receptors.
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Cattle
Enzyme Activation
Female
Humans
Insulin Receptor Substrate Proteins
Lymphoma, T-Cell
Mice
Mice, Inbred BALB C
Phosphoinositide-3 Kinase Inhibitors
Phosphorylation drug effects
Receptor, IGF Type 1 deficiency
Signal Transduction drug effects
Tumor Cells, Cultured drug effects
Tumor Cells, Cultured enzymology
Tyrosine metabolism
Growth Hormone pharmacology
Insulin pharmacology
Mitogens pharmacology
Phosphatidylinositol 3-Kinases metabolism
Phosphoproteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0898-6568
- Volume :
- 15
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 12618213
- Full Text :
- https://doi.org/10.1016/s0898-6568(02)00113-4