Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. 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 (By similarity). ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein] Inhibited by dephosphorylation by PTPN6. Interacts with PTPN11; may activate the PI3 kinase-mTOR signaling pathway. Interacts with VAV3; constitutive interaction mediating VAV3 phosphorylation. Interacts with PTPN6 (via SH2 1 domain); the interaction is direct and promotes ROS1 dephosphorylation (By similarity). Expressed in heart, lung, kidney and testis. Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2266 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation. Phosphorylation at Tyr-2266 stimulates the kinase activity and the activation of the ERK1 signaling cascade. Phosphorylation at Tyr-2266 and/or Tyr-2325 recruits PTPN11 (By similarity). Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.