Functional analysis of ALK, a receptor-type protein tyrosine kinase in axonal regeneration

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06752
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: Machino Masaaki 名古屋大学, 医学部附属病院, 医員 (70807510)
• Research Collaborator: KADOMATSU kenji
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 受容体型チロシンキナーゼ / 未分化リンパ腫キナーゼ / 神経軸索

Outline of Final Research Achievements

Anaplastic lymphoma kinase (ALK) is a receptor type tyrosine kinase (RTK) that is expressed in neurons of the central and peripheral nervous systems. We investigated whether the ASP3026 as inhibitor of ALK and knocking down of ALK by siRNA suppress the outgrowth of adult mouse dorsal root ganglion (DRG) neurons, whether monoclonal antibody (mAb) 16-39 as an agonist of kinase activity of ALK promote axon outgrowth. In cultured DRG neuron, ALK was activated in elongating growth cones and sprouting axonal branches. Inhibition of ALK by ASP3026, reduced axonal elongation and branching in adult neurons. Inactivation of ALK by siRNA, reduced axonal elongation and branching in adult neurons. In contrast, mAb16-39 induced tyrosine phosphorylation of ALK, activation of ALK by mAb16-39, and promoted axonal elongation and sprouting. ALK significantly enhanced axonal elongation and branching. Taken together, our data indicate pivotal roles of RTK pathway in neural development or its repair.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

未分化リンパ腫キナーゼ（ALK）は受容体チロシンキナーゼ（RTK）の1つであり、特定の神経細胞集団に対して増殖、生存維持などの作用を持つ受容体として機能するとされるが、詳しい機能はいまだ不明である。本研究から得られて研究結果はALKの活性を調節している機構を解明し、ALKを標的とする神経再生治療法の開発に寄与する可能性を秘めている。