Transmembrane signalling by insulin via an insulin receptor mutated at tyrosines 1158, 1162, and 1163.
In order to study the role of tyrosine autophosphorylation in insulin receptor signalling, we investigated a mutant human insulin receptor whereby the three major tyrosine autophosphorylation sites at positions 1158, 1162, and 1163 in the receptor beta-subunit were mutated to phenylalanines. When these mutant receptors were expressed in HTC rat hepatoma cells, there was no enhanced beta-subunit autophosphorylation and tyrosine kinase activity. In these cells there was enhanced insulin stimulation of [3H]AIB uptake and [3H]thymidine incorporation when compared to wild type HTC cells. The present study suggests therefore that the presence of the major insulin autophosphorylation sites is not a requirement for insulin stimulation of amino acid transport and mitogenesis.
Rafaeloff
R
R
Division of Diabetes and Endocrine Research, Mount Zion Medical Center University of California, San Francisco 94120.
Maddux
B A
BA
Brunetti
A
A
Sbraccia
P
P
Sung
C K
CK
Patel
R
R
Hawley
D M
DM
Goldfine
I D
ID
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D015870:Gene Expression; D007328:Insulin / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000235:genetics; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000235:genetics*
D000621:Aminoisobutyric Acids; D007328:Insulin; D014443:Tyrosine; D010649:Phenylalanine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D013936:Thymidine