Much of the cell-to-cell communication is facilitated in humans by 58 cell surface receptor tyrosine kinases (RTKs). In a study published in the EMBO Reports, Finnish research team led by Dr. Markku Varjosalo from the Institute of Biotechnology, University of Helsinki, report a systematic mapping of the molecular interactions of the RTKs.
The RTKs are proteins located at the cell surface. In response to stimuli such as growth factors, RTKs phosphorylate specific target proteins within the cell called ‘substrates’ – and by doing so, modulate the substrate activity or functions. Thus, RTKs play central roles in cell-to-cell signalling and are essential in coordinating complex biochemical pathways and cellular processes. RTKs are involved in several diseases, including cancer and developmental disorders.
Despite the central function and key role of RTKs in human diseases, many of them are still poorly characterized. To resolve the lack of systematic knowledge on the RTKs, the researchers from the University of Helsinki applied three complementary methods to map the molecular context and substrate profiles of the RTKs. First, researchers characterized stable binding partners and the RTK-formed protein complexes, and then identified transient and proximal interactions and the RTK substrates. Finally, they studied how the identified RTK interactions depend on its kinase activity.
”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, Dr. Varjosalo states.
The information provided in the study can also help understanding diseases stemming from the abnormal functions of the RTKs.
“The RTKs have proven to be excellent drug targets for therapeutic intervention in the treatment of various diseases, especially cancer,” Dr. Varjosalo states.
The study was financially supported by the Academy of Finland, University of Helsinki, The Sigrid Juselius Foundation, The Emil Aaltonen Foundation, Instrumentarium Science Foundation and the Cancer Foundation Finland.
Original publication: Salokas K, Liu X, Öhman T, Chowdhury I, Gawriyski L, Keskitalo S, and Varjosalo M. Physical and functional interactome atlas of human receptor tyrosine kinases. EMBO Reports, 2022. DOI: 10.15252/embr.202154041
Research Director Markku Varjosalo
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