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An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation

Author

Listed:
  • Katri Vaparanta

    (University of Turku
    University of Turku and Åbo Akademi University)

  • Anne Jokilammi

    (University of Turku
    University of Turku and Åbo Akademi University)

  • Mahlet Tamirat

    (Åbo Akademi University)

  • Johannes A. M. Merilahti

    (University of Turku
    University of Turku and Åbo Akademi University)

  • Kari Salokas

    (University of Helsinki)

  • Markku Varjosalo

    (University of Helsinki)

  • Johanna Ivaska

    (University of Turku and Åbo Akademi University
    University of Turku
    University of Turku
    University of Turku)

  • Mark S. Johnson

    (Åbo Akademi University)

  • Klaus Elenius

    (University of Turku
    University of Turku and Åbo Akademi University
    University of Turku
    Turku University Hospital)

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.

Suggested Citation

  • Katri Vaparanta & Anne Jokilammi & Mahlet Tamirat & Johannes A. M. Merilahti & Kari Salokas & Markku Varjosalo & Johanna Ivaska & Mark S. Johnson & Klaus Elenius, 2022. "An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34539-4
    DOI: 10.1038/s41467-022-34539-4
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    Cited by:

    1. Kewei Qin & Shuhan Yu & Yang Liu & Rongtian Guo & Shiya Guo & Junjie Fei & Yuemeng Wang & Kaiyuan Jia & Zhiqiang Xu & Hu Chen & Fengtian Li & Mengmeng Niu & Mu-Shui Dai & Lunzhi Dai & Yang Cao & Yujun, 2023. "USP36 stabilizes nucleolar Snail1 to promote ribosome biogenesis and cancer cell survival upon ribotoxic stress," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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