A pathway map of AXL receptor-mediated signaling network
- PDF / 722,915 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 68 Downloads / 218 Views
NUTS AND BOLTS
A pathway map of AXL receptor-mediated signaling network Shobha Dagamajalu 1 & D. A. B. Rex 1 & Akhina Palollathil 1 & Rohan Shetty 2 & Guruprasad Bhat 3 & Lydia W. T. Cheung 4 & T. S. Keshava Prasad 1 Received: 24 July 2020 / Accepted: 17 August 2020 # The International CCN Society 2020
Introduction 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). AXL activation is mediated by a ligand called growth arrest-specific protein 6 (GAS6), which is the product of GAS6 gene. GAS6 is a vitamin-K dependent growth factor mainly express in multiple cells (Sasaki et al. 2006). GAS6 has the highest affinity for AXL among the TAM family members. The stimulation of AXL receptor by binding of GAS6 induces receptor dimerization and subsequently AXL activation, which transfers signals from the extracellular matrix into the cytoplasm and results in various signaling pathways through its downstream substrates. The activation of
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12079-020-00580-5) contains supplementary material, which is available to authorized users. Shobha Dagamajalu and D. A. B. Rex contributed equally to this work. * Shobha Dagamajalu [email protected] * T. S. Keshava Prasad [email protected]
Lydia W. T. Cheung [email protected] 1
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India
2
Department of Surgical Oncology, Yenepoya Medical College, Yenepoya (Deemed to be University), Mangalore 575018, India
3
Department of Medical
Data Loading...
