Two naturally occurring insulin receptor tyrosine kinase domain mutants provide evidence that phosphoinositide 3-kinase activation alone is not sufficient for the mediation of insulin's metabolic and mitogenic effects.

@article{Krook1997TwoNO,
  title={Two naturally occurring insulin receptor tyrosine kinase domain mutants provide evidence that phosphoinositide 3-kinase activation alone is not sufficient for the mediation of insulin's metabolic and mitogenic effects.},
  author={A. Krook and Jonathan Whitehead and Scott Dobson and Matthew R Griffiths and Margriet Ouwens and Cheryl Baker and Alice C. Hayward and Soumitra Kumar Sen and Johannes A Maassen and Kenneth Siddle and Jeremy Tavare and Stephen O'Rahilly},
  journal={The Journal of biological chemistry},
  year={1997},
  volume={272 48},
  pages={30208-14}
}
We have recently reported (1) that two naturally occurring mutants of the insulin receptor tyrosine kinase domain, Arg-1174 --> Gln and Pro-1178 --> Leu (Gln-1174 and Leu1178, respectively), both found in patients with inherited severe insulin resistance, markedly impaired receptor tyrosine autophosphorylation, with both mutant receptors being unable to mediate the stimulation of glycogen synthesis or mitogenesis by insulin when expressed in Chinese hamster ovary cells. However, these mutations… CONTINUE READING