PXD026617-1

PXD026617 is an original dataset announced via ProteomeXchange.

Title	Targeted validation of interaction between ErbB4 JM-a isoform and β1 integrin
Description	The ErbB4 receptor isoforms JM-a and JM-b differ within their extracellular juxtamembrane (eJM) domains. Here we used ErbB4 isoforms as a model to address whether structural variation in the eJM domain of receptor tyrosine kinases (RTK) affects downstream signaling. Analysis of ErbB4 interactome and super-resolution cell imaging indicated association of the JM-a- and JM-b-like receptors with specific signaling complexes at different cell surface compartments. A JM-a-specific sequence motif was discovered, and its presence in the eJM domains of several other human RTKs predicted selective STAT activation indicating a conserved RTK signaling mechanism. The RTKs with the JM-a-like eJM motif activated STAT5a, and those that were JM-b-like (lacking the JM-a-like motif) activated STAT5b and STAT3. TYK2 was found to be necessary for JM-b-stimulated STAT5b activation. The activation of STAT5a by the JM-a-like receptors, in turn, involved specific interaction with oligosaccharides N-linked to cell surface glycoproteins such as β1 integrin. These findings provide evidence for a mechanism linking a ubiquitous extracellular motif in RTKs with selective intracellular STAT signaling.
HostingRepository	PanoramaPublic
AnnounceDate	2022-10-22
AnnouncementXML	Submission_2022-10-22_22:33:13.759.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Johannes Merilahti
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-10 06:53:26	ID requested
⏵ 1	2022-10-22 22:33:14	announced

Dataset with its publication pending

submitter keyword: ErbB4, JM-a, JM-b, STAT signaling, Receptor tyrosine kinase

Klaus Elenius
contact affiliation	Medicity Research Laboratories and Institute of Biomedicine, Faculty of Medicine, University of Turku, Finland. Turku Bioscience Centre, University of Turku and Åbo Akademi University, Finland
contact email	klaus.elenius@utu.fi
lab head
Johannes Merilahti
contact affiliation	Turku Bioscience Centre, University of Turku and Åbo Akademi University, Finland
contact email	johannes.merilahti@utu.fi
dataset submitter

Panorama Public dataset URI