TYRO3 protein tyrosine kinase | Elisa - Clia - Antibody - Protein

Background

TYRO3, a member of the TAM receptor tyrosine kinase family, plays a critical role in various cellular processes, including cell survival, proliferation, and immune regulation. The TAM family consists of three receptors: TYRO3, AXL, and MERTK, all of which are characterized by their involvement in modulating immune responses and maintaining tissue homeostasis. TYRO3 is encoded by the TYRO3 gene located on chromosome 15q15 in humans and is widely expressed in tissues such as the brain, reproductive organs, and the immune system. Understanding the structural and functional properties of TYRO3 is crucial for elucidating its roles in health and disease.

Protein Structure

TYRO3 is a type I transmembrane protein comprising several distinct domains:

• Extracellular Domain: This region includes two immunoglobulin-like (Ig-like) domains followed by two fibronectin type III (FNIII) domains. The Ig-like domains are involved in ligand binding, primarily interacting with growth arrest-specific protein 6 (GAS6) and protein S, which serve as ligands for TYRO3.
• Transmembrane Domain: This hydrophobic segment anchors the receptor in the cell membrane, allowing it to function as a bridge for signal transduction from the extracellular environment to the intracellular signaling pathways.
• Intracellular Kinase Domain: The cytoplasmic portion of TYRO3 contains the tyrosine kinase domain, which becomes activated upon ligand binding. This activation triggers a cascade of downstream signaling pathways that regulate various cellular processes, including cell survival, proliferation, and differentiation.

Classification and Subtypes

TYRO3 is one of the three members of the TAM receptor family, alongside AXL and MERTK. These receptors share structural similarities but have distinct functional roles and expression patterns:

1. TYRO3: Primarily involved in brain function, reproductive processes, and immune regulation. It has a broad tissue distribution and is implicated in neuroprotection and the regulation of the immune response.
2. AXL: Known for its role in cancer progression, immune suppression, and resistance to therapy. It is overexpressed in various malignancies and contributes to tumorigenesis and metastasis.
3. MERTK: Plays a crucial role in clearing apoptotic cells and maintaining immune tolerance. It is essential for retinal homeostasis and is implicated in certain autoimmune diseases and cancer.

Function and Biological Significance

TYRO3 functions through its interaction with ligands such as GAS6 and protein S, leading to receptor dimerization and autophosphorylation. This activation initiates several downstream signaling pathways, including:

• PI3K-AKT Pathway: Promotes cell survival and growth by activating the serine/threonine kinase AKT, which regulates apoptosis and cell cycle progression.
• MAPK Pathway: Involved in cell proliferation and differentiation by activating mitogen-activated protein kinases (MAPKs).
• NF-κB Pathway: Regulates immune responses and inflammation by activating nuclear factor-kappa B (NF-κB), which controls the transcription of inflammatory cytokines.

TYRO3 is essential for various physiological processes:

• Neuroprotection: In the central nervous system, TYRO3 is involved in protecting neurons from apoptosis and promoting myelination. It helps in maintaining neural integrity and function.
• Immune Regulation: TYRO3 modulates immune responses by regulating the activity of immune cells such as macrophages and dendritic cells. It is involved in clearing apoptotic cells and maintaining immune tolerance to prevent autoimmunity.
• Reproductive Health: TYRO3 is expressed in reproductive tissues, where it plays a role in spermatogenesis and fertility.

Clinical Issues

Dysregulation of TYRO3 is associated with various pathological conditions:

• Cancer: Overexpression of TYRO3 has been observed in several types of cancer, including breast, lung, and melanoma. TYRO3 promotes tumor cell survival, proliferation, and metastasis, making it a potential target for cancer therapy.
• Autoimmune Diseases: Deficient TYRO3 signaling can lead to impaired clearance of apoptotic cells, resulting in the accumulation of cellular debris and the development of autoimmune conditions such as systemic lupus erythematosus (SLE).
• Neurological Disorders: Given its role in neuroprotection, alterations in TYRO3 function are implicated in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis. TYRO3 deficiency can lead to increased neuronal apoptosis and demyelination.

Summary

TYRO3 is a crucial member of the TAM receptor tyrosine kinase family, with significant roles in neuroprotection, immune regulation, and reproductive health. Its structure, comprising extracellular Ig-like and FNIII domains, a transmembrane domain, and an intracellular kinase domain, enables it to mediate essential signaling pathways. Dysregulation of TYRO3 is linked to cancer, autoimmune diseases, and neurological disorders, highlighting its importance in maintaining cellular and tissue homeostasis. As research advances, targeting TYRO3 may offer therapeutic potential for various diseases, emphasizing the need for a comprehensive understanding of its biological functions and clinical implications.