@article{oai:jichi-ir.repo.nii.ac.jp:00000089,
 author = {Bolormaa, Enkhtuvshin and Tamemoto, Hiroyuki and Nagashima, Shuichi and Bayasgalan, Tumenbayar and Sakai, Kento and Osuga, Jun-ichi and Takahashi, Manabu and Tominaga, Shin-ichi and Ishibashi, Shun},
 journal = {自治医科大学紀要, Jichi Medical University Journal},
 month = {Mar},
 note = {Background
Mutations in the tyrosine kinase domain of the insulin receptor gene cause a monogenic syndrome of insulin resistance in humans. The first β strand in this kinase domain is close to the nucleotide binding loop, and its length is conserved through several species. To test whether the exact length of this region is essential for the kinase activity of the insulin receptor, we constructed a one-amino-acid deletion mutant in the first β strand of the tyrosine kinase domain.
Methods
Deletion of Arg1000 with concomitant substitution of Glu1001 to Gln (R1000E1001→Q) was generated by sitedirected mutagenesis. Chinese hamster ovary cells were transfected with mutant or wild-type human insulin receptor cDNA, and stable clones with similar binding activity were screened by insulin binding assay and used for further experiments. Receptor expression, kinase activity and downstream insulin signaling were examined by western blot analysis.
Results
Mature insulin receptor expression was comparable between the wild-type and mutant cells. The mutant insulin receptor showed markedly defective tyrosine kinase activity. Akt kinase phosphorylation was severely reduced, indicating that downstream insulin signaling was also impaired by the mutant receptor.
Conclusion
This study suggests that the deletion of one residue in the first β strand results in a distortion of the optimal positioning of the kinase structure, thereby compromising the kinase activity of the},
 pages = {1--8},
 title = {Critical role of the length of the first β strand in insulin receptor kinase activity},
 volume = {38},
 year = {2016}
}