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- Title
Dermatan sulphate is an activating ligand of anaplastic lymphoma kinase.
- Authors
Machino, Masaaki; Gong, Yuanhao; Ozaki, Tomoya; Suzuki, Yuji; Watanabe, Eri; Imagama, Shiro; Kadomatsu, Kenji; Sakamoto, Kazuma
- Abstract
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that harbours a tyrosine kinase domain in its intracellular region and is expressed in both central and peripheral nervous systems. RTKs are activated upon ligand binding and receptor clustering; however, ALK remains an orphan receptor despite its pathological significance, especially in malignancy. Recent biochemical work showed that heparan sulphate (HS), an unbranched sulphated glycan, acts as a ligand for and activates ALK. Here, we show that dermatan sulphate (DS, chondroitin sulphate B) directly interacts with the extracellular N-terminal region of ALK as well as HS. The tetrasaccharide of DS was required and was sufficient for inducing autophosphorylation of ALK at tyrosine 1604, a marker for activated ALK. Interestingly, longer oligosaccharides caused enhanced activation of ALK, as was the case for HS. Our results provide a novel example of glycans as signalling molecules and shed light on the pathophysiological roles of ALK.
- Subjects
DERMATAN sulfate; ANAPLASTIC lymphoma kinase; PROTEIN-tyrosine kinases; PERIPHERAL nervous system; LIGAND binding (Biochemistry); CENTRAL nervous system; N-terminal residues
- Publication
Journal of Biochemistry, 2021, Vol 170, Issue 5, p631
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/jb/mvab085