Conformational changes of epidermal growth factor receptor induced by binding of different ligands

Receptor za epidermalni faktor rasta je jedan u nizu tirozin kinaznih receptora stanične membrane koji vezanjem specifičnih liganada inducira aktivaciju nizvodnih signalnih puteva koji za rezultat imaju proliferaciju diferencijaciju, migraciju i supresiju apoptoze u stanici. Znajući da se strukturna konformacija receptora mijenja ovisno o vezanom ligandu tijekom procesa internalizacije receptora, cilj ovog rada je ispitati razlike u konformaciji kinaznih domena u sklopu homo/heterodimera inducirane dvjema čimbenicima rasta, tj. izvanstaničnim ligandima EGF i TGF-alfa, te sa i bez pristunosti negativnog regulatora iz citosola, Mig6. Ispitivanje se provodilo na transfektiranim CHO-K1 stanicama iz kojih su se izolirani proteini analizirali pomoću Western blot metode. Istraživanje je pokazalo da se kontakti u kinaznim domenama homodimera razlikuju ovisno o vezanom ligandu te da su kontakti u heterodimerima različiti od onih u homodimerima.The epidermal growth factor receptor is one in a series of transmembrane tyrosine kinase receptors that, by binding specific ligands, induce the activation of downstream signaling pathways that result in proliferation, differentiation, migration, and apoptosis suppression of the cell. Knowing that the structural conformation of the receptor changes depending on the bound ligand during the receptor internalization process, the aim of this study is to examine differences in the conformation of kinase domains within homo/heterodimers induced by different growth factors, i.e. extracellular ligands EGF and TGF-alfa, and with or without the presence of a negative regulator from cytosol, Mig6. The assay was performed on transfected CHO-K1 cells from which isolated proteins were analyzed using the Western blot method. The study showed that the contacts in the kinase domains of homodimers differ depending on the bound ligand and that the contacts in heterodimers are different from those in homodimers