Signaling through the ALK receptor is activated by the bindi...

created [InstanceEdit:9842653] Rothfels, Karen, 2023-08-27
dbId 9842664
displayName Signaling through the ALK receptor is activated by the bindi...
modified [InstanceEdit:9851214] Rothfels, Karen, 2023-10-14
schemaClass Summation
text Signaling through the ALK receptor is activated by the binding of ALKAL ligand to the receptor extracellular region (Zhang et al, 2014; Guan et al, 2015; Reshetnyak et al, 2015; Reshetnyak et al, 2018; Reshetnyak et al, 2021; De Munck et al, 2021).
There are two human ALKAL proteins, ALKAL1 (also known as FAM150A) and ALKAL2 (also known as FAM150B). ALKAL1 and 2 were initially characterized as ligands for the ALK-related receptor leukocyte tyrosine kinase (LTK), and subsequently shown to bind to ALK as well (Zhang et al, 2014; Guan et al, 2015). Further studies revealed differences in ligand affinity for the two receptors, however, likely mediated by the differences in the extracellular domains of the two receptors. Although LTK is potently activated by both ALKAL1 and 2, robust activation of ALK in physiological contexts is only seen with ALKAL2 (Guan et al, 2015; Reshetnyak et al, 2015).
There is conflicting evidence as to whether ALKAL2 binds ALK as a monomer ((De Munck et al, 2021) or a dimer (Reshetnyak et al, 2018; Reshetnyak et al 2021). In this pathway, ALKAL2 is depicted as binding ALK as a dimer linked by interchain disulphide bond at residue C66 (Reshetnyak et al, 2018; Reshetnyak et al, 2021). Binding of ALKAL2 to the ALK receptor is also facilitated by binding of heparin to ALK (De Munck et al, 2021).
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