ALK the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)

Stephan W. Morris, Clayton Naeve, Prasad Mathew, Payton L. James, Mark N. Kirstein, Xiaoli Cui, David P. Witte

Research output: Contribution to journalArticlepeer-review

440 Scopus citations

Abstract

Anaplastic Lymphoma Kinase (ALK) was originally identified as a member of the insulin receptor subfamily of receptor tyrosine kinases that acquires transforming capability when truncated and fused to nucleophosmin (NPM) in the t(2;5) chromosomal rearrangement associated with non-Hodgkin's lymphoma, but further insights into its normal structure and function are lacking. Here, we characterize a full-length normal human ALK cDNA and its product, and determine the pattern of expression of its murine homologue in embryonic and adult tissues as a first step toward the functional assessment of the receptor. Analysis of the 6226 bp ALK cDNA identified an open reading frame encoding a 1620-amino acid (aa) protein of predicted mass ~ 177 kDa that is most closely related to leukocyte tyrosine kinase (LTK), the two exhibiting 57% aa identity and 71% similarity over their region of overlap. Biochemical analysis demonstrated that the ~ 177 kDa ALK polypeptide core undergoes co-translational N-linked glycosylation, emerging in its mature form as a 200 kDa single chain receptor. Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane, consistent with the prediction that ALK serves as the receptor for an unidentified ligand(s). In situ hybridization studies revealed Alk expression beginning on embryonic day 11 and persisting into the neonatal and adult periods of development. Alk transcripts were confined to the nervous system and included several thalamic and hypothalamic nuclei; the trigeminal, facial, and acoustic cranial ganglia; the anterior horns of the spinal cord in the region of the developing motor neurons; the sympathetic chain; and the ganglion cells of the gut. Thus, ALK is a novel orphan receptor tyrosine kinase that appears to play an important role in the normal development and function of the nervous system.

Original languageEnglish (US)
Pages (from-to)2175-2188
Number of pages14
JournalOncogene
Volume14
Issue number18
DOIs
StatePublished - 1997

Bibliographical note

Funding Information:
This research was supported in part by grants CA-01702 and CA-69129 (SWM) and Cancer Center Support (CORE) grant CA-21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities (AL-SAC), St Jude Children’s Research Hospital.

Keywords

  • Anaplastic lymphoma kinase (ALK)
  • Chromosome 2
  • Leukocyte tyrosine kinase (LTK)
  • Neural-specific
  • Receptor tyrosine kinase

Fingerprint

Dive into the research topics of 'ALK the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)'. Together they form a unique fingerprint.

Cite this