Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and genetic interactions in learning, memory and adult neurogenesis

Pharmacol Biochem Behav. 2012 Jan;100(3):566-74. doi: 10.1016/j.pbb.2011.10.024. Epub 2011 Nov 4.


Anaplastic Lymphoma Kinase (Alk) is a receptor tyrosine kinase expressed throughout the adult mammalian hippocampus. Recent studies in Drosophila and prior studies in Caenorhabditis elegans have implicated Alk signaling in learning and neurogenesis. We have studied the roles of Alk and the closely related receptor Leukocyte Tyrosine Kinase (Ltk) in learning, behavior and neurogenesis. In the hippocampus, both receptors are expressed throughout the dentate gyrus, CA1 and CA3. To assess the functional roles of Alk and Ltk in the mammalian brain, we analyzed phenotypes in Alk mutant, Ltk mutant and Alk/Ltk double-mutant mice compared to wild-type littermates. Similar to Drosophila, we found enhanced performance in spatial memory in Alk mutant mice. Also similar to Drosophila, we observed reduced neurogenesis associated with loss of Alk function. We also report genetic interactions between Alk and Ltk with respect to neurogenesis and behavioral measures such as activity, anxiety levels, and retention of spatial memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Animals
  • Anxiety / genetics
  • Behavior, Animal
  • Gene Expression Regulation, Enzymologic
  • Hippocampus / cytology
  • Hippocampus / enzymology*
  • Hippocampus / metabolism
  • Learning*
  • Male
  • Memory*
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Motor Activity
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis*
  • Neurons / cytology
  • Neurons / enzymology*
  • Neurons / metabolism
  • Organ Specificity
  • RNA, Messenger / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Spatial Behavior


  • Nerve Tissue Proteins
  • RNA, Messenger
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • Ltk protein, mouse
  • Receptor Protein-Tyrosine Kinases