A pathway map of AXL receptor-mediated signaling network

摘要

AXL is a transmembrane protein that comes under TAM (TYRO3,AXL and MERTK) family of receptor tyrosine kinases (RTKs) (Myers et al. 2019). It is first identified as a transforming gene isolated from primary human myeloid leukemia cells (O’Bryan et al. 1991). The AXL gene is located in chromosome 19, at 19q13.1(Linz et al. 1993), which encodes a protein of 894 amino acids (Korshunov 2012). AXL receptor has an extracellular, a transmembrane and an intracellular domains. The extracellular domain contains two immunoglobulin-like (IgL) and fibronectin type-III (FN III)- like domains with a single-pass transmembrane domain (Linger et al. 2008). The intracellular tyrosine kinase domain of AXL contains six phosphorylation sites. Among these three phosphorylation sites were in C-terminal domain (Tyr779, Tyr821 and Tyr866) and others in N-terminal domain (Tyr698, Tyr702, Tyr703). Autophosphorylation of C-terminal phosphorylation sites stimulated by GAS6 has a role in the kinase activity of AXL (Linger et al. 2008, O’Bryan et al. 1991). Phosphorylation of the residues in the N-terminal domain induced by GAS6 has also been shown (Pao-Chun et al. 2009). In particular, phosphorylated Tyr702 may stabilize the conformation of the activation loop of AXL, promoting AXL activity (PMID: 28,724,631). AXL is known to extensively express in various tissues such as brain, heart, liver, bone marrow, neurons and vascular tissues (Jin et al. 2015, Lemke 2013, Lemke and Rothlin 2008, Nielsen-Preiss et al. 2007).