Phosphorylation Effects on Flanking Charged Residues

Structural Implications for Signal Transduction in Protein Kinases

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

1H‐NMR and 31P‐NMR spectroscopy were employed to assess the electrostatic consequences of phosphorylation of single and multiple tyrosine residues in peptides derived from the core and tail autophosphorylation regions of the human insulin receptor tyrosine‐kinase domain. In both peptides, phosphorylation was accompanied by changes in the resonances from basic side‐chains; those from acidic residues were unaffected. Tyrosine phosphorylation caused increases of up to one in the pKa values of histidine residues situated up to eight residues away in the primary sequence. Titration curve analysis by Hill plots suggested some cooperativity of histidine and phosphate ionizations. Behaviour closely analogous to that of the insulin receptor tail peptide was observed during changes in phosphorylation of the intact insulin receptor kinase domain, suggesting that the electrostatic dissemination effects seen for the isolated peptide are retained by the peptide sequence in the context of the much larger protein. Similar changes in the behaviour of basic residues were also observed upon tyrosine phosphorylation of a cdc2‐derived peptide, suggesting that this potential of phosphorylation events to propagate directed structural changes may find a widespread utility in the activation of protein kinases and in the transduction of phosphorylation‐based signalling.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalEuropean Journal of Biochemistry
Volume224
Issue number1
DOIs
StatePublished - 1994
Externally publishedYes

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Signal transduction
Phosphorylation
Protein Kinases
Signal Transduction
Peptides
Tyrosine
Insulin Receptor
Static Electricity
Histidine
Electrostatics
Titration
Ionization
Spectrum Analysis
Phosphotransferases
Chemical activation
Phosphates
Spectroscopy
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphorylation Effects on Flanking Charged Residues : Structural Implications for Signal Transduction in Protein Kinases. / Chavanieu, Alain; Keane, Noeleen E.; Quirk, Philip G.; Levine, Barry A.; Calas, Bernard; Wei, Lei; Ellis, Leland.

In: European Journal of Biochemistry, Vol. 224, No. 1, 1994, p. 115-123.

Research output: Contribution to journalArticle

Chavanieu, Alain ; Keane, Noeleen E. ; Quirk, Philip G. ; Levine, Barry A. ; Calas, Bernard ; Wei, Lei ; Ellis, Leland. / Phosphorylation Effects on Flanking Charged Residues : Structural Implications for Signal Transduction in Protein Kinases. In: European Journal of Biochemistry. 1994 ; Vol. 224, No. 1. pp. 115-123.
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