kinasesTYRO3

TYRO3, also known as Tyro3 receptor tyrosine kinase, is a member of the TAM receptor family that also includes AXL and MERTK. It functions as a cell surface receptor activated by the ligands Gas6 and Protein S, which bridge phosphatidylserine on apoptotic cells to the receptor. Upon ligand binding and receptor phosphorylation, TYRO3 initiates intracellular signaling that modulates cell behavior.

The TYRO3 protein has an extracellular region containing two immunoglobulin-like domains and two fibronectin type III repeats, a single-pass transmembrane segment, and an intracellular tyrosine kinase domain. It is expressed across multiple tissues and cell types, with notable presence in neural cells (neurons, astrocytes, oligodendrocytes), and in various immune cells such as dendritic cells and monocytes, as well as platelets and endothelial cells. Expression patterns can be context-dependent, varying with development and physiological state.

Functionally, TYRO3 participates in the clearance of apoptotic cells (efferocytosis) and helps regulate immune responses to prevent excessive inflammation. Activation of TYRO3 triggers signaling pathways including PI3K/Akt, MAPK/ERK, and STAT cascades, leading to outcomes such as enhanced phagocytosis, survival signals, and induction of regulatory mechanisms (for example, SOCS1/3) that dampen inflammatory cytokine production. In the central nervous system, TYRO3 contributes to glial support and myelination, as well as neuronal survival, while in the immune system it contributes to maintaining self-tolerance.

Clinical and research relevance includes associations with autoimmune regulation in animal models, and the potential involvement of TYRO3 signaling in cancer, where it can support tumor cell survival and modulate tumor-associated immune responses. As a result, TAM receptor signaling is an area of interest for therapies aiming to modulate immune activity and tumor progression.