Kinase inhibition by a phosphorylated peptide corresponding to the major insulin receptor autophosphorylation domain

Chavanieu, Alain; Calas, Bernard; Vaglio, Philippe; Grigorescu, Florin

doi:10.1111/j.1432-1033.1992.tb17196.x

Cited by 5 publications

(4 citation statements)

References 42 publications

(10 reference statements)

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“…Peptide synthesis was carried out on a fluorenemethoxycarbonyl (Fmoc) PAL-PEG resin, or a Fmoc Arg(Pmc)-PEG resin (Millipore), by Fmoc strategy on an automatic apparatus (9050 Pepsynthesiser, Milligen). Peptide synthesis was performed as described elsewhere [9]. Then, the crude peptide-amide was precipitated with ether, filtered and dried in a desiccator.…”

Section: Peptide Synthesmentioning

confidence: 99%

Change in membrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation

et al. 1996

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Protegrin 1 (PG-1) is a naturally occurring cationic antimicrobial peptide that is 18 residues long, has an aminated carboxy terminus and contains two disulphide bridges. Here, we investigated the antimicrobial activity of PG-1 and three linear analogues. Then, the membrane permeabilisation induced by these peptides was studied upon Xenopus laevis oocytes by electrophysiological methods. From the results obtained, we concluded that protegrin is able to form anion channels. Moreover, it seems clear that the presence of disulphide bridges is a prerequisite for the pore formation at the membrane level and not for the antimicrobial activity.

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Section: Peptide Synthesmentioning

confidence: 99%

Change in membrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation

et al. 1996

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Section: Peptide Synthesis and Purificationmentioning

confidence: 99%

“…The phosphorylated peptide RRDIYETDYpYRK (YYpY) was synthesised using the FmocTyr-0-PO,-(benzyl), method (Chavanieu et al, 1992). Subsequent deblocking and HPLC purification of all peptides were performed as previously described (Chavanieu et al, 1991(Chavanieu et al, , 1992, except that the anion-exchange chromatography step was omitted. The composition of each peptide was confirmed after acid hydrolysis using a Beckman Model 6300 amino acid analyser, and additionally analysed by electrospray mass spectrometry (VG TRIO 2000, Fison Instruments) as well as by two-dimensional NMR methods.…”

Section: Peptide Synthesis and Purificationmentioning

confidence: 99%

Phosphorylation Effects on Flanking Charged Residues

Chavanieu

Keane

Quirk

et al. 1994

European Journal of Biochemistry

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*H-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 pK, 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.Reversible protein phosphorylation is the most common cellular regulation mechanism. Phosphorylation is associated with a stereochemical influence on the equilibrium distribution of conformational states of the protein, which results in a net change in the average protein structure. Two mechanisms of phosphoregulation have so far been recognised: allosteric regulation in phosphorylase, where phosphorylation induces a domain rotation (reviewed by Johnson, 1992), and, as exemplified by isocitrate dehydrogenase, direct control mediated principally by electrostatic effects at the active site, thereby modulating substrate binding (Hurley et al., 1989).The recently determined structure of a phosphoregulated kinase (ERK2) (Zhang et al., 1994) suggests that a combination of these two paradigm mechanisms underlies the regulation of catalytic activity common to many kinases, a large number of which require multisite phosphorylation to trigger kinase activity. One such example is the human insulin receptor Correspondence to B. A. Levine,

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“…This region is located close to the active site in known PTK structures and has been dubbed as the regulatory segment in kinase activation (Marshall, 1994). In the case of the insulin receptor, the corresponding peptide is indeed an effective inhibitor of autophosphorylation (Cobb et al, 1989;Shoelson et al, 1989;Chavanieu et al, 1992). Two further sites of tyrosine autophosphorylation are located in the IRPTK C-terminal tail region (Tyr1328 and Tyr1334).…”

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confidence: 99%

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

Keane¹,

Chavanieu²,

Quirk³

et al. 1994

European Journal of Biochemistry

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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.

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Kinase inhibition by a phosphorylated peptide corresponding to the major insulin receptor autophosphorylation domain

Cited by 5 publications

References 42 publications

Change in membrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation

Change in membrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation

Phosphorylation Effects on Flanking Charged Residues

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

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