Transactivation of PDGFRbeta by dopamine D4 receptor does not require PDGFRbeta dimerization.
Growth factor-induced receptor dimerization and cross-phosphorylation are hallmarks of signal transduction via receptor tyrosine kinases (RTKs). G protein-coupled receptors (GPCRs) can activate RTKs through a process known as transactivation. The prototypical model of RTK transactivation involves ligand-mediated RTK dimerization and cross-phosphorylation. Here, we show that the platelet-derived growth factor receptor beta (PDGFRbeta) transactivation by the dopamine receptor D4 (DRD4) is not dependent on ligands for PDGFRbeta. Furthermore, when PDGFRbeta dimerization is inhibited and receptor phosphorylation is suppressed to near basal levels, the receptor maintains its ability to be transactivated and is still effective in signaling to ERK1/2. Hence, the DRD4-PDGFRbeta-ERK1/2 pathway can occur independently of a PDGF-like ligand, PDGFRbeta cross-phosphorylation and dimerization, which is distinct from other known forms of transactivation of RTKs by GPCRs.
Chi
Sum Shing
SS
Department of Neuroscience, Centre for Addiction and Mental Health, University of Toronto, Toronto M5T 1R8, Canada.
Vetiska
Sandra M
SM
Gill
Robin S
RS
Hsiung
Marilyn S
MS
Liu
Fang
F
Van Tol
Hubert Hm
HH
D000818:Animals; D000077214:Becaplermin; D002460:Cell Line; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050638:Receptors, Dopamine D4; D000077214:Becaplermin; D019000:Phosphotyrosine; D020797:Receptor, Platelet-Derived Growth Factor beta; D048049:Extracellular Signal-Regulated MAP Kinases; D004298:Dopamine