The oncogenic fusion protein EML4-NTRK3 requires three salt bridges for stability and biological activity.

ABSTRACT:

Aim of study

Chromosomal translocations involving neurotrophic receptor tyrosine kinases (NTRKs) have been identified in 20 % of soft tissue sarcomas. This work focuses on the EML4-NTRK3 translocation identified in cases of Infantile Fibrosarcoma, which contains the coiled-coil multimerization domain of Echinoderm Microtubule-like protein 4 (EML4) fused with the tyrosine kinase domain of Neurotrophic Receptor Tyrosine Kinase 3 (NTRK3). The aim of the study was to test the importance of tyrosine kinase activity and multimerization for the oncogenic activity of EML4-NTRK3.

Methods

These studies examined EML4-NTRK3 proteins containing a kinase-dead or WT kinase domain, together with mutations in specific salt bridge residues within the coiled-coil domain. Biological activity wa

SUBMITTER: Jiang Z 

PROVIDER: S-EPMC11381775 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature