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Functional co-operation between the subunits in heterodimeric platelet-derived growth factor receptor complexes

Emaduddin, Muhammad; Ekman, Simon; Rönnstrand, Lars LU and Heldin, Carl-Henrik (1999) In Biochemical Journal 341(3). p.523-528
Abstract
To determine the importance of the phosphorylation capacity of receptor kinase as well as the ability to serve as docking sites for SH2-domain-containing signal transduction molecules, we established pig aortic endothelial cell lines stably expressing kinase-active platelet-derived growth factor (PDGF) alpha-receptors together with kinase-inactive beta-receptors, and vice versa. After stimulation with PDGF-AB, heterodimeric receptor complexes were formed in which the kinase-inactive receptor was phosphorylated by the kinase-active receptor, although less efficiently than in heterodimers of wild-type receptors. The kinase-active receptor was only minimally phosphorylated. Thus the phosphorylation within the receptor dimer occurred in trans... (More)
To determine the importance of the phosphorylation capacity of receptor kinase as well as the ability to serve as docking sites for SH2-domain-containing signal transduction molecules, we established pig aortic endothelial cell lines stably expressing kinase-active platelet-derived growth factor (PDGF) alpha-receptors together with kinase-inactive beta-receptors, and vice versa. After stimulation with PDGF-AB, heterodimeric receptor complexes were formed in which the kinase-inactive receptor was phosphorylated by the kinase-active receptor, although less efficiently than in heterodimers of wild-type receptors. The kinase-active receptor was only minimally phosphorylated. Thus the phosphorylation within the receptor dimer occurred in trans between the components. Analyses of the abilities of heterodimeric receptor complexes of one kinase-active and one kinase-inactive receptor to mediate mitogenicity, chemotaxis and activation of mitogen-activated protein kinase revealed less efficient effects than those of heterodimers of wild-type receptors. Importantly, however, the fact that signalling capacities were retained illustrates a functional co-operation between the two receptor molecules in the dimer, where one receptor provides a functional kinase and the other acts as a substrate and provides docking sites for downstream signalling molecules. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Platelet-Derived Growth Factor/*metabolism *Signal Transduction Swine Tyrosine/metabolism, Animals Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Line Cell Movement/drug effects DNA Primers Dimerization Enzyme Activation Mitogens/pharmacology Peptide Mapping Phosphorylation Platelet-Derived Growth Factor/pharmacology Receptors
in
Biochemical Journal
volume
341
issue
3
pages
523 - 528
publisher
Portland Press Limited
external identifiers
  • scopus:0033179048
ISSN
0264-6021
language
English
LU publication?
no
id
7227e1c8-1d33-4f6c-9966-e0b7a36dcce8 (old id 1782696)
alternative location
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220387/
date added to LUP
2011-02-07 17:25:51
date last changed
2017-05-07 04:29:54
@article{7227e1c8-1d33-4f6c-9966-e0b7a36dcce8,
  abstract     = {To determine the importance of the phosphorylation capacity of receptor kinase as well as the ability to serve as docking sites for SH2-domain-containing signal transduction molecules, we established pig aortic endothelial cell lines stably expressing kinase-active platelet-derived growth factor (PDGF) alpha-receptors together with kinase-inactive beta-receptors, and vice versa. After stimulation with PDGF-AB, heterodimeric receptor complexes were formed in which the kinase-inactive receptor was phosphorylated by the kinase-active receptor, although less efficiently than in heterodimers of wild-type receptors. The kinase-active receptor was only minimally phosphorylated. Thus the phosphorylation within the receptor dimer occurred in trans between the components. Analyses of the abilities of heterodimeric receptor complexes of one kinase-active and one kinase-inactive receptor to mediate mitogenicity, chemotaxis and activation of mitogen-activated protein kinase revealed less efficient effects than those of heterodimers of wild-type receptors. Importantly, however, the fact that signalling capacities were retained illustrates a functional co-operation between the two receptor molecules in the dimer, where one receptor provides a functional kinase and the other acts as a substrate and provides docking sites for downstream signalling molecules.},
  author       = {Emaduddin, Muhammad and Ekman, Simon and Rönnstrand, Lars and Heldin, Carl-Henrik},
  issn         = {0264-6021},
  keyword      = {Platelet-Derived Growth Factor/*metabolism
*Signal Transduction
Swine
Tyrosine/metabolism,Animals
Base Sequence
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
Cell Line
Cell Movement/drug effects
DNA Primers
Dimerization
Enzyme Activation
Mitogens/pharmacology
Peptide Mapping
Phosphorylation
Platelet-Derived Growth Factor/pharmacology
Receptors},
  language     = {eng},
  number       = {3},
  pages        = {523--528},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Functional co-operation between the subunits in heterodimeric platelet-derived growth factor receptor complexes},
  volume       = {341},
  year         = {1999},
}