Growth inhibition signalled through the interleukin-4/interleukin-13 receptor complex is associated with tyrosine phosphorylation of insulin receptor substrate-1.
Induction of growth inhibition in human colorectal carcinoma cell lines by interleukin (IL)-4 and IL-13 was associated with the neophosphorylation of a 170 kDa cellular protein, identified as insulin receptor substrate-1 (IRS-1) by immunoprecipitation. Tyrosine phosphorylation of IRS-I was also induced by insulin and insulin-like growth factor I. Sublines of colorectal carcinoma cells unresponsive to growth modulation by IL-4, IL-13 or insulin-like growth factor I-induced growth did not phosphorylate IRS-1. A functional, multimeric IL-4 receptor complex was present on all carcinoma cell lines with a subunit composition of 65 kDa, 75 kDa and the previously characterized 130 kDa band as demonstrated by affinity cross-link with 126I labelled IL-4. The 65 kDa subunit is novel whereas the 75 kDa band represents the common IL-2 receptor gama-chain the novel 65 kDa receptor was present as a double band and bound primarily 125I-labelled IL-13. The present study demonstrates the involvement of a novel chain other than the gama-chain in the receptor complexes of IL-4 and IL-13 and and post-receptor tyrosine phosphorylation of IRS-1. The association of IRS-1 with growth inhibitory signals in carcinoma cells suggests a novel mechanism of tumour growth control.
Schnyder
B
B
Institute of Toxicology, Swiss Federal Institute of Technology, Switzerland.
Lahm
H
H
Woerly
G
G
Odartchenko
N
N
Ryffel
B
B
Car
B D
BD
D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003432:Cross-Linking Reagents; D015536:Down-Regulation; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D018793:Interleukin-13 / Q000494:pharmacology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D046911:Macromolecular Substances; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011869:Radioligand Assay; D018123:Receptors, Interleukin / Q000737:chemistry / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000737:chemistry
D015703:Antigens, CD; D003432:Cross-Linking Reagents; C508181:IL13RA1 protein, human; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D046911:Macromolecular Substances; D010750:Phosphoproteins; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D014443:Tyrosine