AXL signaling (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="AXL signaling pathway" Version="03132020" Author="Rex D. A. B, Shobha" Maintainer="Dr. Keshava Prasad" Email="keshav@yenepoya.edu.in" Organism="Homo sapiens"> <Comment>March_2020</Comment> <Comment>Type your comment here</Comment> <Comment Source="WikiPathways-description">Axl is a transmembrane protein comes under TAM (Tyro3,Axl and Mertk) family of receptor tyrosine kinase (RTK). It is first identified as transforming gene, isolated from primary human myeloid leukemia cells. Axl gene is located in chromosome 19, at 19q13.1 , which encodes 894 amino acids with molecular weight range between 100 and 140kDa. Axl receptor is having extracellular, transmembrane and an intracellular domain. Extra cellular domain contains two immunoglobulin like (IgL) and fibronectin type-III (FN III) like domain with a single pass transmembrane domain. </Comment> <Comment Source="WikiPathways-description">Axl is a transmembrane protein comes under TAM (Tyro3,Axl and Mertk) family of receptor tyrosine kinase (RTK). It is first identified as transforming gene, isolated from primary human myeloid leukemia cells. Axl gene is located in chromosome 19, at 19q13.1 , which encodes 894 amino acids with molecular weight range between 100 and 140kDa. Axl receptor is having extracellular, transmembrane and an intracellular domain. Extra cellular domain contains two immunoglobulin like (IgL) and fibronectin type-III (FN III) like domain with a single pass transmembrane domain. An intracellular protein tyrosine kinase domain contains total six phosphorylation sites, among them three phosphorylation sites were found in N-terminal domain such as Tyr 779 , Tyr 821 and Tyr 866 and other three sites were found in C-terminal domain such as Tyr 698 , Tyr 702 , Tyr 703 which are getting autophosphorlyated to accomplish their complete functions of subsequent kinase activity. Axl activation is mediated by a ligand growth arrest-specific protein 6 (Gas6). The activation of Axl can also occur through ligand independent in response to ROS which mainly occurs during oxidative stress and overexpression of Axl. Axl receptor is extensively expressed in various tissues such as brain, heart, liver, bone marrow, neurons and vascular tissues. The aberrant expression as well as prolonged activation of Axl has been reported in various disease conditions such as cancer, chronic immune disorders and cardiovascular diseases. The Axl receptor is a class of protein that transfer signals from the extracellular matrix into the cytoplasm and results in various signaling pathways through its downstream substrates. This regulates various physiological processes including cell proliferation, survival, motility, aggregation and anti-inflammation. The Axl receptor activation contributes various down signaling pathways including PI3K/AKT, MAPK/ERK, JAK/STAT, and PI3K/AKT/mTOR. Axl ligand independent activation also induces AKT and MAPK signaling pathways and regulates EMT, which are mainly involved in cell proliferation, migration and survival of colorectal cancer. However, it has a major concern in biomedical importance, comprehensive detail about Axl mediated signaling pathway is still unavailable in the publically available pathway resources. Therefore, we systematically developed an integrated pathway map of Axl signaling. The pathway map was developed through literature mining from published literature data based on manual annotation guidelines adapted from Netpath (curated resource of signal transduction pathways in humans). In the present study, PubMed search using query terms showed about 1170 articles, which were related to Axl signaling pathway until November 2019. These articles were carefully reviewed based on our annotation criteria and short listed into 171 articles which had information pertinent to Axl mediated signaling.</Comment> <Attribute Key="org.pathvisio.sbgn.language" Value="process description" /> <Graphics BoardWidth="4005.165561634761" BoardHeight="2410.1775147928997" /> <DataNode TextLabel="MYC" GraphId="a859f" Type="GeneProduct"> <Graphics CenterX="1614.5427276533815" CenterY="1396.2345125823704" Width="80.0" Height="20.0" ZOrder="32768" FontWeight="Bold" FontStyle="Italic" FontSize="12" Valign="Middle" /> <Xref Database="" ID="MYC" /> </DataNode> <DataNode TextLabel="ANXA2" GraphId="aa51c" Type="GeneProduct"> <Graphics CenterX="769.3224066665183" CenterY="1628.210627528125" Width="80.0" Height="20.0" ZOrder="32768" FontWeight="Bold" FontStyle="Italic" FontSize="12" Valign="Middle" /> <Xref Database="" ID="ANXA2" /> </DataNode> <DataNode TextLabel="ATG5" GraphId="aeded" Type="GeneProduct"> <Graphics CenterX="2049.400064993528" 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