Physical and functional interactome atlas of human receptor tyrosine kinases.

Autor: Salokas K; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland., Liu X; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland., Öhman T; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland., Chowdhury I; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland., Gawriyski L; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland., Keskitalo S; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland., Varjosalo M; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2022 Jun 07; Vol. 23 (6), pp. e54041. Date of Electronic Publication: 2022 Apr 05.
DOI: 10.15252/embr.202154041
Abstrakt: Much cell-to-cell communication is facilitated by cell surface receptor tyrosine kinases (RTKs). These proteins phosphorylate their downstream cytoplasmic substrates in response to stimuli such as growth factors. Despite their central roles, the functions of many RTKs are still poorly understood. To resolve the lack of systematic knowledge, we apply three complementary methods to map the molecular context and substrate profiles of RTKs. We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates. To identify how kinase interactions depend on kinase activity, we also use kinase-deficient mutants. Our data represent a comprehensive, systemic mapping of RTK interactions and substrates. This resource adds information regarding well-studied RTKs, offers insights into the functions of less well-studied RTKs, and highlights RTK-RTK interactions and shared signaling pathways.
(© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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