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Updated: Aug 23, 2026

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
Published on: October 30, 2018
ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth
Akira Motegi1, Jiro Fujimoto, Masaharu Kotani
1Division of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Japan.
Abstract:
Anaplastic lymphoma kinase (ALK) is a receptor-type protein tyrosine kinase that is expressed preferentially in neurons of the central and peripheral nervous systems at late embryonic stages. To elucidate the role of ALK in neurons, we developed an agonist monoclonal antibody (mAb) against the extracellular domain of ALK. Here we show that mAb16-39 elicits tyrosine phosphorylation of endogenously expressed ALK in human neuroblastoma (SK-N-SH) cells. Stimulation of these cells with mAb16-39 markedly induces the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), Shc, and c-Cbl and also their interaction with ALK and activation of ERK1/2. Furthermore, we show that continuous incubation with mAb16-39 induces the cell growth and neurite outgrowth of SK-N-SH cells. These responses are completely blocked by MEK inhibitor PD98059 but not by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, indicating an essential role of the mitogen-activated protein kinase (MAP kinase) signaling cascade in ALK-mediated growth and differentiation of neurons.
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