Overview:

ROS1 is a proto-oncogene and member of the sevenless subfamily of tyrosine kinase insulin receptor genes. ROS1 is highly-expressed in a variety of tumor cell lines and functions as a growth or differentiation factor receptor. The FIG gene can fuse with the ROS1 gene in glioblastoma cell lines (1). The resulting ROS1/FIG fusion protein is a constitutively activated tyrosine kinase. Direct interaction of ROS1 and the phosphatase SHP-1 can lead to efficient downregulation of ROS1-mediated signaling (2). Binding sites in the ROS1 cytoplasmic domain display high affinity binding to the SHP-1 N-terminal SH2 domain. Structural models of ROS1 (L2086F) predict resistance to crizotinib, entrectinib, and lolartanib via steric hindrance (3).

References:

1. Charest, A. et al: Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21). Genes Chromosomes Cancer 37: 58-71, 2003.
2. Biscup, C. et al: Visualization of SHP-1-target interaction. J Cell Sci. 2004 Oct 1;117(Pt 21):5165-78. 3. Gendarme, S. et al: ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date. Curr. Oncol. 29(2):641-658, 2022.