ALK Gene

Last updated on: 12.12.2021

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Definition
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ALK is the acronym for "Anaplastic Lymphoma Kinase. The ALK gene is a biologically important protein-coding gene located on chromosome 2p23.2-p23.1. The gene encodes anaplastic lymphoma kinase, a phosphorylase. This enzyme phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. ALK acts as a receptor for the ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a pleiotrophin-related factor.

Binding of pleiotrophin to ALK leads to activation of the MAPK pathway, which is important for the anti-apoptotic signaling effect of pleiotrophin and regulation of cell proliferation. MDK binding induces phosphorylation of ALK target substrate, insulin receptor (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3 kinases, which also leads to induction of cell proliferation. ALK controls NF-kappa-B activation, likely via IRS1 and activation of the serine/threonine kinase AKT. Recruitment of IRS1 to activated ALK and activation of NF-kappa-B are essential for midkine autocrine growth and survival signaling.

Note(s)
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ALK is being studied in the context of obesity because a gene knockout of ALK in mice leads to decreased triglycerides but increased free fatty acids and glycerol in the blood and these mice become resistant to food-induced obesity.

Literature
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  1. Hallberg B et al (2016) The role of the ALK receptor in cancer biology. Ann Oncol 27 Suppl 3:iii4-iii15.
  2. Huang H (2018) Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase: A catalytic receptor with many faces. Int J Mol Sci 19:3448.
  3. Iqbal Jet al. (2014) Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood123:2915-2923.
  4. Mossé YP et al (2017) Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study. J Clin Oncol 35:3215-3221.
  5. Sgambato A et al. (2018) Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors. Expert Rev Anticancer Ther 18:71-80.

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Last updated on: 12.12.2021