Structural Determinants of Substrate Selection by the Human Insulin‐Receptor Protein‐Tyrosine Kinase

Noeleen E. Keane, Alain Chavanieu, Philip G. Quirk, James S. Evans, Barry A. Levine, Bernard Calas, Lei Wei, Leland Ellis

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Using NMR spectroscopy to visualise tyrosine phosphorylation kinetics in real time, we have investigated the sequence‐dependent determinants of the selectivity of the human insulin receptor protein‐tyrosine kinase for different tyrosine residues. The peptides used encompass the multipletyrosine‐containing autophosphorylation site sequences from the insulin receptor kinase core domain (Tyr1158, Tyr162 and Tyr1163) and from its specific C‐terminal tail domain (Tyr1328 and Tyr1334). Comparison of the phosphorylation kinetics with those found for the tyrosine residues on a peptide comprising the regulatory tyrosine phosphorylation site of cdc2 points to the role of the primary sequence context of the phosphate acceptor. The particularly deleterious influence of a basic residue immediately C‐terminal to the tyrosine is discussed in relation to the autophosphorylation properties of the regulatory loop regions of the insulin and epidermal growth factor receptor kinases. The data further suggest that receptor tyrosine kinase active sites and their substrate targets act in concert to ensure that specific downstream effects are activated.

Original languageEnglish (US)
Pages (from-to)525-536
Number of pages12
JournalEuropean Journal of Biochemistry
Issue number2
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Biochemistry

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