Abstract
AbstractThe 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.
Funder
Finnish Cultural Foundation | Varsinais-Suomen Rahasto
Finnish Cultural Foundation | Keski-Suomen Rahasto
Sydäntutkimussäätiö
Emil Aaltosen Säätiö
Maud Kuistilan Muistosäätiö
Orionin Tutkimussäätiö
K. Albin Johanssons Stiftelse
Syöpäsäätiö
Syöpäjärjestöt
Turku University Foundation
The Foundation of Åbo Akademi Joe, Pentti and Tor Borg Memorial Fund
Academy of Finland
Sigrid Juséliuksen Säätiö
Turun Yliopistollinen Keskussairaala
Turun Yliopisto
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Cited by
3 articles.
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