title: Multiple tyrosine residues in the intracellular domain of the common beta subunit of the interleukin 5 receptor are involved in activation of STAT5.
abstract: In contrast to the general model of cytokine-induced JAK/STAT signaling, tyrosine phosphorylation of the IL-5R beta chain seems to be dispensable for STAT activation in cells overexpressing exogenous STAT proteins. In this study we expressed IL-5 receptor mutants in 293 cells and studied IL-5-induced endogenous STAT-dependent transcription. Our results indicate that: (a) tyrosine phosphorylation of the IL-5R beta chain is required for endogenous STAT5 activation, (b) multiple tyrosine residues are phosphorylated upon IL-5 stimulation, including Tyr577, Tyr612, Tyr695, and Tyr750, and (c) Tyr612, Tyr695, and Tyr750 are all capable of inducing activation of STAT5, demonstrating a high level of functional redundancy within the IL-5R beta chain.
authors.affiliation: Department of Pulmonary Diseases, University Hospital Utrecht, Netherlands.
authors.forename: T B
authors.initials: TB
authors.lastname: van Dijk
authors.forename: E
authors.initials: E
authors.lastname: Caldenhoven
authors.forename: J A
authors.initials: JA
authors.lastname: Raaijmakers
authors.forename: J W
authors.initials: JW
authors.lastname: Lammers
authors.forename: L
authors.initials: L
authors.lastname: Koenderman
authors.forename: R P
authors.initials: RP
authors.lastname: de Groot
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015848:Interleukin-5 / Q000494:pharmacology; D051379:Mice; D008894:Milk Proteins; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D053649:Receptors, Interleukin-5; D050799:STAT5 Transcription Factor; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D015848:Interleukin-5; D008894:Milk Proteins; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014443:Tyrosine