Functional co-operation between the subunits in heterodimeric platelet-derived growth factor receptor complexes
Författare
Summary, in English
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.
Publiceringsår
1999
Språk
Engelska
Sidor
523-528
Publikation/Tidskrift/Serie
Biochemical Journal
Volym
341
Issue
3
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Portland Press
Ämne
- Medicinal Chemistry
Nyckelord
- Platelet-Derived Growth Factor/*metabolism*Signal TransductionSwineTyrosine/metabolism
- AnimalsBase SequenceCalcium-Calmodulin-Dependent Protein Kinases/metabolismCell LineCell Movement/drug effectsDNA PrimersDimerizationEnzyme ActivationMitogens/pharmacologyPeptide MappingPhosphorylationPlatelet-Derived Growth Factor/pharmacologyReceptors
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0264-6021