Details

Autor(en) / Beteiligte

• Machino, Masaaki
• Gong, Yuanhao
• Ozaki, Tomoya
• Suzuki, Yuji
• Watanabe, Eri
• Imagama, Shiro
• Kadomatsu, Kenji
• Sakamoto, Kazuma

Titel

Dermatan sulphate is an activating ligand of anaplastic lymphoma kinase

Ist Teil von

• Journal of biochemistry (Tokyo), 2021-11, Vol.170 (5), p.631-637

Ort / Verlag

England

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.