Identification of a biologically active fragment of ALK and LTK-Ligand 2 (augmentor-α)

Abstract

Significance The limited availability of the two ligands of the receptor tyrosine kinases ALK and LTK precluded the elucidation of their physiological roles and mechanism of action. In this report we describe two new approaches to produce full-length ALKAL2/AUG-α and an active variant lacking the N-terminal variable region. Detailed characterization of the primary structure and disulfide bridges using mass spectrometry demonstrates that the N-terminal variable region plays an important role in AUG-α dimerization and provides insight into the structural organization of a previously unknown augmentor fold. A variety of cellular experiments show that both AUG-α and its deletion mutant induce similar activation of ALK and LTK and stimulation neuronal differentiation of human neuroblastoma NB1 and rat pheochromocytoma PC12 cells.