ROS1
Function
Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous stimulation by NELL2, ROS1 activates the intracellular signaling pathway and triggers epididymal epithelial differentiation and subsequent sperm maturation (By similarity). May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.
Involvement in disease
A chromosomal aberration involving ROS1 is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which is localized to the Golgi and has a constitutive receptor tyrosine kinase activity. A SLC34A2-ROS1 chimeric protein produced in non-small cell lung cancer cells also retains a constitutive kinase activity. A third type of chimeric protein CD74-ROS1 was also identified in those cells.
Post-translational modifications
Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2274 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation. Phosphorylation at Tyr-2274 stimulates the kinase activity and the activation of the ERK1 signaling cascade (By similarity). Phosphorylation at Tyr-2274 and/or Tyr-2334 recruits PTPN11 (PubMed:12538861).
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Tissue Specificity
Expressed in brain. Expression is increased in primary gliomas.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
Alternative names
MCF3, ROS, ROS1, Proto-oncogene tyrosine-protein kinase ROS, Proto-oncogene c-Ros, Proto-oncogene c-Ros-1, Receptor tyrosine kinase c-ros oncogene 1, c-Ros receptor tyrosine kinase