A unique autophosphorylation site in the platelet-derived growth factor alpha receptor from a heterodimeric receptor complex
Rupp, Eva ; Siegbahn, Agneta ; Rönnstrand, Lars LU
; Wernstedt, Christer
; Claesson-Welsh, Lena
and Heldin, Carl-Henrik
(1994)
In European Journal of Biochemistry
225(1).
p.29-41
- Abstract
- The platelet-derived growth factor (PDGF) alpha and beta receptors undergo dimerization as a consequence of ligand binding. Depending on the PDGF isoform (PDGF-AA, -AB or -BB), homodimers or heterodimers of receptors are formed. In this study, we have used transfected porcine aortic endothelial cells, coexpressing cDNAs for the alpha receptor and the beta receptor at comparable levels, to investigate the properties of the alpha beta-heterodimeric receptor complex. PDGF-AB, which mainly induced alpha beta-heterodimeric complexes, was the most efficient isoform for stimulating mitogenicity. Actin reorganization, in the form of circular membrane ruffling and chemotaxis, was induced by PDGF-AB and PDGF-BB, but not by PDGF-AA, thus indicating... (More)
- The platelet-derived growth factor (PDGF) alpha and beta receptors undergo dimerization as a consequence of ligand binding. Depending on the PDGF isoform (PDGF-AA, -AB or -BB), homodimers or heterodimers of receptors are formed. In this study, we have used transfected porcine aortic endothelial cells, coexpressing cDNAs for the alpha receptor and the beta receptor at comparable levels, to investigate the properties of the alpha beta-heterodimeric receptor complex. PDGF-AB, which mainly induced alpha beta-heterodimeric complexes, was the most efficient isoform for stimulating mitogenicity. Actin reorganization, in the form of circular membrane ruffling and chemotaxis, was induced by PDGF-AB and PDGF-BB, but not by PDGF-AA, thus indicating that the beta receptor in the homodimeric or heterodimeric configuration was required for induction of motility responses. The molecular basis for the apparent receptor dimer-specific properties was examined by analyzing receptor autophosphorylation and phosphorylation of substrates. The alpha receptor was found to be phosphorylated at an additional tyrosine residue, Tyr754, in the heterodimeric complex as compared to the alpha alpha receptor homodimer. Phosphorylation of this tyrosine residue could permit the binding of a specific signal-tranducing protein. A candidate is a 134,000-M(r) protein, which was shown to associate preferentially with the alpha receptor in the heterodimeric receptor complex. It is possible that phosphorylated Tyr754 in the alpha receptor mediates activation of specific signal-tranducing molecules like the 134,000-M(r) substrate, and thereby initiates signal-tranduction pathways from the alpha beta receptor heterodimer, which are distinct from those initiated via homodimeric receptor complexes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1783985
- author
- Rupp, Eva
; Siegbahn, Agneta
; Rönnstrand, Lars
LU
; Wernstedt, Christer
; Claesson-Welsh, Lena
and Heldin, Carl-Henrik
- publishing date
- 1994
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Platelet-Derived Growth Factor/*chemistry/*metabolism Recombinant Proteins/chemistry/metabolism Swine Transfection Tyrosine/analogs & derivatives/analysis, Platelet-Derived Growth Factor alpha Receptor, Platelet-Derived Growth Factor beta Receptors, Cultured Endothelium, Amino Acid Sequence Animals Aorta Binding Sites Cells, Vascular/cytology/drug effects/*metabolism Humans Kinetics Macromolecular Substances Molecular Sequence Data Phosphates/metabolism Phosphopeptides/chemistry/isolation & purification Phosphorylation Phosphotyrosine Platelet-Derived Growth Factor/metabolism/*pharmacology Receptor
- in
- European Journal of Biochemistry
- volume
- 225
- issue
- 1
- pages
- 29 - 41
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:0028136094
- ISSN
- 0014-2956
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- d90fb21f-8a01-4d0f-b553-1e4f1450edaf (old id 1783985)
- date added to LUP
- 2016-04-04 09:43:58
- date last changed
- 2021-01-10 05:37:30
@article{d90fb21f-8a01-4d0f-b553-1e4f1450edaf,
abstract = {{The platelet-derived growth factor (PDGF) alpha and beta receptors undergo dimerization as a consequence of ligand binding. Depending on the PDGF isoform (PDGF-AA, -AB or -BB), homodimers or heterodimers of receptors are formed. In this study, we have used transfected porcine aortic endothelial cells, coexpressing cDNAs for the alpha receptor and the beta receptor at comparable levels, to investigate the properties of the alpha beta-heterodimeric receptor complex. PDGF-AB, which mainly induced alpha beta-heterodimeric complexes, was the most efficient isoform for stimulating mitogenicity. Actin reorganization, in the form of circular membrane ruffling and chemotaxis, was induced by PDGF-AB and PDGF-BB, but not by PDGF-AA, thus indicating that the beta receptor in the homodimeric or heterodimeric configuration was required for induction of motility responses. The molecular basis for the apparent receptor dimer-specific properties was examined by analyzing receptor autophosphorylation and phosphorylation of substrates. The alpha receptor was found to be phosphorylated at an additional tyrosine residue, Tyr754, in the heterodimeric complex as compared to the alpha alpha receptor homodimer. Phosphorylation of this tyrosine residue could permit the binding of a specific signal-tranducing protein. A candidate is a 134,000-M(r) protein, which was shown to associate preferentially with the alpha receptor in the heterodimeric receptor complex. It is possible that phosphorylated Tyr754 in the alpha receptor mediates activation of specific signal-tranducing molecules like the 134,000-M(r) substrate, and thereby initiates signal-tranduction pathways from the alpha beta receptor heterodimer, which are distinct from those initiated via homodimeric receptor complexes.}},
author = {{Rupp, Eva and Siegbahn, Agneta and Rönnstrand, Lars and Wernstedt, Christer and Claesson-Welsh, Lena and Heldin, Carl-Henrik}},
issn = {{0014-2956}},
keywords = {{Platelet-Derived Growth Factor/*chemistry/*metabolism
Recombinant Proteins/chemistry/metabolism
Swine
Transfection
Tyrosine/analogs & derivatives/analysis; Platelet-Derived Growth Factor alpha
Receptor; Platelet-Derived Growth Factor beta
Receptors; Cultured
Endothelium; Amino Acid Sequence
Animals
Aorta
Binding Sites
Cells; Vascular/cytology/drug effects/*metabolism
Humans
Kinetics
Macromolecular Substances
Molecular Sequence Data
Phosphates/metabolism
Phosphopeptides/chemistry/isolation & purification
Phosphorylation
Phosphotyrosine
Platelet-Derived Growth Factor/metabolism/*pharmacology
Receptor}},
language = {{eng}},
number = {{1}},
pages = {{29--41}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Biochemistry}},
title = {{A unique autophosphorylation site in the platelet-derived growth factor alpha receptor from a heterodimeric receptor complex}},
volume = {{225}},
year = {{1994}},
}