Naslov
Mapping and functional characterization of the ErbB receptor tyrosine kinase family using the Mammalian Membrane Two-Hybrid Assay

Autori
Vučetić, Adriana

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad, diplomski

Fakultet
Prirodoslovno-matematički fakultet

Mjesto
Zagreb

Datum
12.12

Godina
2017

Stranica
73

Mentor
Štagljar, Igor

Neposredni voditelj
Franjević, Damjan

Ključne riječi
ErbB2, PPI, SH2 domain, PTB domain, MaMTH

Sažetak
Around 30% of all proteins in cells are membrane proteins, which have important biological functions. Receptor tyrosine kinases (RTKs) are a family of transmembrane receptors that mediate different cell responses to extracellular stimulus. One of the most studied subfamilies of RTKs, the ErbB family, is related to many human diseases and members are targets for the development of new therapeutics. The ErbB family consists of four members (ErbB1-4) that share similar protein structures. Upon ligand binding to the extracellular domain, two molecules of receptor dimerize, which leads to activation of the intracellular kinase domain and autophosphorylation of the C-terminal tail. The resulting phosphotyrosines are recruitment sites for proteins that typically bind through Src homology-2 (SH2) or phosphotyrosine-binding (PTB) domains and provide specific stimulation of downstream pathways. Molecular mechanisms implicated in disease pathology commonly include aberrant protein-protein interactions (PPIs), which make the understanding of PPIs very significant for developing effective therapies. The aim of this study was to map and characterize interactions between the ErbB2 receptor tyrosine kinase and proteins which contain SH2 and/or PTB domains, using the MaMTH assay, a novel proteomics approach suitable for mapping interactions of membrane proteins. Thirty-six interacting proteins were identified, binding through the SH2 domain was characterized for ErbB2-Sla2 and ErbB2-Crk2, and potential PPIs implicated in aberrant signaling were detected.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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