Novel insight into mechanisms of ROS1 catalytic activation via loss of the extracellular domain.

ABSTRACT: The ROS1 receptor tyrosine kinase (RTK) possesses the largest extracellular amino-terminal domain (ECD) among the human RTK family, yet the mechanisms regulating its activation are not fully understood. While chimeric ROS1 fusion proteins, resulting from chromosomal rearrangements, are well-known oncogenic drivers, their activation mechanisms also remain underexplored. To elucidate the role of the ROS1 ECD in catalytic regulation, we engineered a series of amino-terminal deletion mutants. Our functional studies compared the full-length ROS1 receptor, the CD74-ROS1 oncogenic fusion, and ECD-deleted ROS1 constructs, identifying the ECD regions that inhibit ROS1 tyrosine kinase activity. Notably, we found that deletion of the ROS1 ECD alone significantly increases constitutive catalytic activ

SUBMITTER: Jones K 

PROVIDER: S-EPMC11437283 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature