TYRO3


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TYRO3

A gene on chromosome 15q15.1 that encodes a receptor tyrosine kinase which transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands (e.g., TUB, TULP1 or GAS6), regulating various physiological processes including cell survival, cell migration and differentiation. It also plays a key role in inhibiting Toll-like receptor-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signalling SOCS1 and SOCS3.
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The expression of TAM receptors showed diverse expressions: while LPS downregulated the expression of TYRO3 and MERTK, it significantly induced the expression of AXL (Figures 4(a) and 4(b)).
de Kouchkovsky et al., "The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity," Science, vol.
Calarese et al., "Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and complex regulation of ligand-induced activation," The Journal of Biological Chemistry, vol.
The relative gene expression of TAM receptors Tyro3 (a), Axl (b), and Mertk (c) and their ligands Gas6 (d) and Prosl (e) as well as the EMT-inducer Snail (f) is shown from control (left columns, n = 2), uninflamed (middle columns, n = 6), and inflamed (right columns, n = 6) rat colon sections.
The relative gene expression of TAM receptors TYRO3 (a), AXL (b), and MERTK (c); their receptors GAS6 (d) and PROS1 (e); and genes involved in epithelial-to-mesenchymal transition SNAI1 (f), ZEB2 (g), MMP9 (h), CDH1 (i), VIM (j), and HIF1a (k) as well as microRNA miR-192 (l) are shown from inactive (left, n = 5), active-uninflamed (middle, n = 7), and active-inflamed (right, n = 5) colon samples of IBD patients.
The relative gene expression of the proinflammatory molecule TNF[alpha], TAM receptors TYRO3, AXL, and MERTK, and the suppressor of cytokine signalling SOCS-3 in (a) inactivated LPS-stimulated THP-1, (b) PMA-activated LPS-stimulated THP-1, and (c) TNF[alpha]-stimulated HT-29 cells.
In some experiments, cardiac tissue was used as positive control for Axl, and kidney tissue was used as positive control for Tyro3 and Mertk.
The expression of TAM receptors (Tyro3, Axl, and Mertk) in mouse [CD4.sup.+][CD25.sup.+]Tregs was determined by Western blot.
Gas6 is the ligand for the TAM family of receptors, which is composed of 3 members: Tyro3, Axl, and Mertk [8, 9].
Vermeij et al., "Therapeutic efficacy of Tyro3, Axl, and Mertk tyrosine kinase agonists in collagen-induced arthritis," Arthritis & Rheumatology, vol.
RXDX-106 is a novel oral immunomodulatory agent with potent nonclinical antitumor activity that appears to restore and enhance overall immune function by reversing immunosuppression of innate immune cells in the tumor microenvironment (TME) through inhibition of the receptor tyrosine kinases (RTKs) TYRO3, AXL, and MER.