An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation

Katri Vaparanta, Anne Jokilammi, Mahlet Tamirat, Johannes A. M. Merilahti, Kari Salokas, Markku Varjosalo, Johanna Ivaska, Mark S. Johnson and Klaus Elenius ()
Additional contact information
Katri Vaparanta: University of Turku
Anne Jokilammi: University of Turku
Mahlet Tamirat: Åbo Akademi University
Johannes A. M. Merilahti: University of Turku
Kari Salokas: University of Helsinki
Markku Varjosalo: University of Helsinki
Johanna Ivaska: University of Turku and Åbo Akademi University
Mark S. Johnson: Åbo Akademi University
Klaus Elenius: University of Turku

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract The ErbB4 receptor isoforms JM-a and JM-b differ within their extracellular juxtamembrane (eJM) domains. Here, ErbB4 isoforms are used as a model to address the effect of structural variation in the eJM domain of receptor tyrosine kinases (RTK) on downstream signaling. A specific JM-a-like sequence motif is discovered, and its presence or absence (in JM-b-like RTKs) in the eJM domains of several RTKs is demonstrated to dictate selective STAT activation. STAT5a activation by RTKs including the JM-a like motif is shown to involve interaction with oligosaccharides of N-glycosylated cell surface proteins such as β1 integrin, whereas STAT5b activation by JM-b is dependent on TYK2. ErbB4 JM-a- and JM-b-like RTKs are shown to associate with specific signaling complexes at different cell surface compartments using analyses of RTK interactomes and super-resolution imaging. These findings provide evidence for a conserved mechanism linking a ubiquitous extracellular motif in RTKs with selective intracellular STAT signaling.

Date: 2022
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34539-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34539-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34539-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().