Browse ALK

Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type I membrane protein Note=Membrane attachment was crucial for promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP kinase pathway.
Domain PF00629 MAM domain
PF07714 Protein tyrosine kinase
Function

Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.

> Gene Ontology
 
Biological Process GO:0000187 activation of MAPK activity
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0032147 activation of protein kinase activity
GO:0033674 positive regulation of kinase activity
GO:0038061 NIK/NF-kappaB signaling
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0045860 positive regulation of protein kinase activity
GO:0046777 protein autophosphorylation
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0004702 receptor signaling protein serine/threonine kinase activity
GO:0004704 NF-kappaB-inducing kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005057 receptor signaling protein activity
GO:0019199 transmembrane receptor protein kinase activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG -
Reactome -
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ALK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between ALK and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
18469826LymphomaPromote immunityThe anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination.
16434370Anaplastic Large Cell LymphomaPromote immunityIn vivo T-cell immune response against anaplastic lymphoma kinase in patients with anaplastic large cell lymphomas. Anaplastic lymphoma kinase (ALK) oncogenic fusion proteins, expressed in about 60% of anaplastic large cell lymphomas (ALCL), are tumor-specific molecular targets for such a malignancy. The high number of anti-ALK memory CD8 T cells present in patients' PBMC may represent a valid source of activated CTL suitable for cancer cell lysis.
27879258Lymphoma; Lung Carcinoma; NeuroblastomaInhibit immunityAnaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically expressed by fetal neural cells. However, aberrantly expressed ALK is involved in the pathogenesis of diverse malignancies, including distinct types of lymphoma, lung carcinoma, and neuroblastoma. NPM-ALK co-opts several intracellular signal transduction pathways, foremost being the STAT3 pathway, normally activated by cytokines from the interleukin-2 (IL-2) family to promote cell proliferation and to inhibit apoptosis. Many genes and proteins modulated by NPM-ALK are also involved in evasion of antitumor immune response. NPM-ALK uses epigenetic silencing mechanisms to downregulate tumor suppressor genes to maintain its own expression. NPM-ALK is capable of transforming primary human CD4+ T cells into immortalized cell lines indistinguishable from patient-derived ALK+ ALCL.
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of ALK in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: -1.64; FDR: 0.02150 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 3 Resistant to T-cell proliferation
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of ALK in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.3310.324
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2170.705
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.7270.134
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1220.715
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.4390.793
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2720.888
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.5720.277
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.3910.667
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.7390.433
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.5810.179
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7540.206
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2090.447
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ALK in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 1417011.8-11.80.488
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103033.3-33.30.231
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.86.880.247
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.88.56.30.453
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.55.93.61
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916012.5-12.50.52
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47028.6-28.60.491
1329033130MelanomaallAnti-PD-1 (nivolumab) 382715.8015.80.037
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221313.6013.60.279
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161418.8018.80.228
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ALK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ALK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ALK.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ALK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ALK expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ALK and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolALK
Nameanaplastic lymphoma receptor tyrosine kinase
Aliases CD246; anaplastic lymphoma kinase (Ki-1); NBLST3; CD246 antigen; mutant anaplastic lymphoma kinase; CD antig ......
Chromosomal Location2p23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ALK collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ALK.
ID Name Drug Type Targets #Targets
DB00171ATPSmall MoleculeABCA1, ABCB1, ABCB11, ABCC1, ABCC2, ABCC4, ABCC6, ABCC8, ABCC9, AB ......42
DB08865CrizotinibSmall MoleculeALK, MET2
DB09063CeritinibSmall MoleculeALK1
DB11363AlectinibSmall MoleculeALK1
DB12267BrigatinibSmall MoleculeABL1, ALK, EGFR, ERBB2, ERBB4, FLT3, IGF1R, INSR, MET9