Identification of an autoinhibitory domain in the insulin receptor tyrosine kinase.

Abstract:

:We have tested the hypothesis that activation of the insulin receptor tyrosine kinase is due to autophosphorylation of tyrosines 1146, 1150 and 1151 within a putative autoinhibitory domain. A synthetic peptide corresponding to residues 1134-1162, with tyrosines substituted by alanine or phenylalanine, of the insulin receptor beta subunit was tested for its inhibitory potency and specificity towards the tyrosine kinase activity. This synthetic peptide gave inhibition of the insulin receptor tyrosine kinase autophosphorylation and phosphorylation of the exogenous substrate poly(Glu, Tyr) with an approximate IC50 of 100 microM. Inhibition appeared to be independent of the concentrations of insulin or the substrate poly(Glu, Tyr) but was decreased by increasing concentrations of ATP. This same peptide also inhibited the EGF receptor tyrosine kinase but not a serine/threonine protein kinase. These results are consistent with the hypothesis that this autophosphorylation domain contains an autoinhibitory sequence.

journal_name

Mol Cell Biochem

authors

Filipek A,Soderling TR

doi

10.1007/BF00926082

subject

Has Abstract

pub_date

1993-03-24 00:00:00

pages

103-10

issue

2

eissn

0300-8177

issn

1573-4919

journal_volume

120

pub_type

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