Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system

Oncogene. 1997 Jan 30;14(4):439-49. doi: 10.1038/sj.onc.1200849.

Abstract

The 2;5 chromosomal translocation is frequently associated with anaplastic large cell lymphomas (ALCLs). The translocation creates a fusion gene consisting of the alk (anaplastic lymphoma kinase) gene and the nucelophosmin (npm) gene: the 3' half of alk derived from chromosome 2 is fused to the 5' portion of npm from chromosome 5. A recent study shows that the product of the npm-alk fusion gene is oncogenic. To help understand how the npm-alk oncogene transform cells, it is important to investigate the normal biological function of the alk gene product, ALK. Here, we show molecular cloning of cDNAs for both the human and mouse ALK proteins. The deduced amino acid sequences reveal that ALK is a novel receptor protein-tyrosine kinase having a putative transmembrane domain and an extracellular domain. These sequences are absent in the product of the transforming npm-alk gene. ALK shows the greatest sequence similarity to LTK (leukocyte tyrosine kinase) whose biological function is presently unknown. RNA blot hybridization analysis of various tissues reveals that the alk mRNA is dominantly detected in the brain and spinal cord. Immunoblotting with anti-ALK antibody shows that ALK is highly expressed in the neonatal brain. Furthermore, RNA in situ hybridization analysis shows that the alk mRNA is dominantly expressed in neurons in specific regions of the nervous system such as the thalamus, mid-brain, olfactory bulb, and ganglia of embryonic and neonatal mice. These data suggest that ALK plays an important role(s) in the development of the brain and exerts its effects on specific neurons in the nervous system.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Anaplastic Lymphoma Kinase
  • Animals
  • Animals, Newborn
  • Base Sequence
  • Brain / embryology
  • Brain / metabolism*
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 5
  • Cloning, Molecular
  • DNA, Complementary
  • Embryo, Mammalian
  • Ganglia / embryology
  • Ganglia / metabolism
  • Gene Expression
  • Gene Library
  • Humans
  • In Situ Hybridization
  • Male
  • Mice
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Organ Specificity
  • Protein-Tyrosine Kinases / biosynthesis*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry
  • Sequence Homology, Amino Acid
  • Spinal Cord / embryology
  • Spinal Cord / metabolism*
  • Testis / metabolism
  • Translocation, Genetic

Substances

  • DNA, Complementary
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • nucleophosmin
  • ALK protein, human
  • Alk protein, mouse
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases

Associated data

  • GENBANK/D83002
  • GENBANK/U66559