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ALK mutants bind TKIs

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-9700645

PubChem

R-HSA-9700645

Description

Aberrant signaling by activated forms of ALK can be inhibited by tyrosine kinase inhibitors (TKIs). ALK, like other tyrosine kinase receptors, is activated through a series of phosphorylation and conformational changes that move the receptor from the inactive form to the fully activated form. Type II TKIs bind to the inactive form of the receptor at a site adjacent to the ATP-binding cleft, while type I TKIs bind to the active form (reviewed in Roskoski, 2013). Type I inhibitors crizotinib, brigatinib, alectinib, ceritinib and lorlatinib are all approved for treatment of ALK-dependent cancer. Development of resistance to TKIs is not uncommon, however, either through acquisition of secondary mutations or through activation of bypass pathways that remove the dependence on ALK signaling (reviewed in Lovly and Pao, 2012; Lin et al, 2017; Della Corte et al, 2018).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 10** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O00291	Huntingtin-interacting protein 1	HIP1	view
P02751	Fibronectin	FN FN1	view
P06748	Nucleophosmin	NPM NPM1	view
P10644	cAMP-dependent protein kinase type I-alpha regulatory subunit	PKR1 PRKAR1 PRKAR1A TSE1	view
Q00610	Clathrin heavy chain 1	CLH17 CLTC CLTCL2 KIAA0034	view
Q9H165	BCL11 transcription factor A	BCL11A CTIP1 EVI9 KIAA1809 ZNF856	view
Q9HC35	Echinoderm microtubule-associated protein-like 4	C2orf2 EMAPL4 EML4	view
Q9NR09	Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6	BIRC6 KIAA1289	view
Q9NZJ5	Eukaryotic translation initiation factor 2-alpha kinase 3	EIF2AK3 PEK PERK	view
Q9UM73	ALK tyrosine kinase receptor	ALK	view

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