Identification of two juxtamembrane autophosphorylation sites in the PDGF β-receptor; involvement in the interaction with Src family tyrosine kinases

Seijiro Mori, Lars Rönnstrand, Koutaro Yokote, Åke Engström, Sara Courtneidge, Lena Claesson-Welsh, Carl Henrik Heldin

Research output: Contribution to journalArticle

285 Citations (Scopus)

Abstract

Two novel sites of autophosphorylation were localized to the juxtamembrane segment of the human plateletderived growth factor (PDGF) β-receptor. To evaluate the importance of these phosphorylation sites, receptor mutants were made in which Tyr579, Tyr581 or both were replaced with phenylalanine residues; the receptor mutants were stably expressed in porcine aortic endothelial cells. Compared with the wild-type receptor, the Y579F and Y581F mutants were less able to mediate association with and activation of the Src family tyrosine kinases. The ability of these phosphorylation sites to mediate directly the binding of the Src family proteins was also demonstrated by using phosphotyrosine-containing synthetic peptides representing the juxtamembrane sequence of the receptor. Both the Y579F and Y581F mutants were similar to the wild-type receptor with regard to their protein tyrosine kinase activity and ability to induce mitogenicity in response to PDGF-BB. A conclusive evaluation of the role of the Src family members in signal transduction could, however, not be made since our attempt to prevent completely the association by mutation of both Tyr579 and Tyr581, resulted in loss of kinase activity and was therefore not informative. The present data, together with previous observations, demonstrate a high degree of specificity in the interaction between different autophosphorylation sites in the PDGF β-receptor and downstream components in the signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)2257-2264
Number of pages8
JournalEMBO Journal
Volume12
Issue number6
StatePublished - 1993
Externally publishedYes

Fingerprint

Signal transduction
Phosphorylation
Aptitude
Growth Factor Receptors
src-Family Kinases
Signal Transduction
Association reactions
Phosphotyrosine
Endothelial cells
Phenylalanine
Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Swine
Endothelial Cells
Chemical activation
Peptides
Mutation
Proteins

Keywords

  • Autophosphorylation
  • PDGF β-receptor
  • Src family tyrosine kinases
  • Src homology 2 domain
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Mori, S., Rönnstrand, L., Yokote, K., Engström, Å., Courtneidge, S., Claesson-Welsh, L., & Heldin, C. H. (1993). Identification of two juxtamembrane autophosphorylation sites in the PDGF β-receptor; involvement in the interaction with Src family tyrosine kinases. EMBO Journal, 12(6), 2257-2264.

Identification of two juxtamembrane autophosphorylation sites in the PDGF β-receptor; involvement in the interaction with Src family tyrosine kinases. / Mori, Seijiro; Rönnstrand, Lars; Yokote, Koutaro; Engström, Åke; Courtneidge, Sara; Claesson-Welsh, Lena; Heldin, Carl Henrik.

In: EMBO Journal, Vol. 12, No. 6, 1993, p. 2257-2264.

Research output: Contribution to journalArticle

Mori, S, Rönnstrand, L, Yokote, K, Engström, Å, Courtneidge, S, Claesson-Welsh, L & Heldin, CH 1993, 'Identification of two juxtamembrane autophosphorylation sites in the PDGF β-receptor; involvement in the interaction with Src family tyrosine kinases', EMBO Journal, vol. 12, no. 6, pp. 2257-2264.
Mori, Seijiro ; Rönnstrand, Lars ; Yokote, Koutaro ; Engström, Åke ; Courtneidge, Sara ; Claesson-Welsh, Lena ; Heldin, Carl Henrik. / Identification of two juxtamembrane autophosphorylation sites in the PDGF β-receptor; involvement in the interaction with Src family tyrosine kinases. In: EMBO Journal. 1993 ; Vol. 12, No. 6. pp. 2257-2264.
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