Abstract
The leukocyte tyrosine kinase (LTK) and anaplastic lymphoma kinase (ALK) receptor tyrosine kinases (RTKs) define a subgroup of the insulin receptor superfamily. Leukocyte tyrosine kinase (LTK) was initially discovered by screening a mouse pre-B-lymphocyte library with the avian v-ros gene [1]. Subsequent work revealed the presence of an LTK extracellular domain [2], but it required significant further cloning efforts to clearly define the structure of this RTK. Cloning of the full-length LTK receptor revealed an intracellular PTK domain accompanied by a 347-amino-acid extracellular domain, which is relatively small when compared with other members of the receptor kinase superfamily. The LTK cDNA was subsequently shown to encode a glycosylated receptor harbouring in vitro kinase activity (Fig. 1.1) [3, 4].
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Acknowledgment
Bengt Hallberg and Ruth Palmer have financial support for research from the Swedish Cancer Society, the Children’s Cancer Foundation, the Swedish Research Council, Swedish Foundation for Strategic Research and the JC Kempe Foundation.
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Appendix
Appendix
Receptor at a glance: ALK/LTK
Chromosome location | ALK, 2p23; LTK, 15q15.1 |
Gene size (bp) | ALK, 728,793; LTK, 10,303 |
Intron/exon numbers | ALK, 29 exons; LTK, 20 exons |
mRNA size | ALK, 6,267; LTK, several mRNA forms, predominant 3,046 |
Amino acid number | ALK, 1620 a.a; LTK, 864 a.a. |
kDa | ALK, 176 kDa; LTK, 91 kDa |
Post-translational modifications | ALK: glycosylated, phosphorylated LTK: glycosylated, phosphorylated |
Domains | ALK: MAM, LDLa, glycine-rich domain, kinase domain LTK: glycine-rich domain, kinase domain |
Ligands | ALK: unclear (Jeb and HEN-1 in Drosophila and C. elegans; no Jeb-like ligand reported in mammalians as yet) LTK: FAM150A and B |
Known dimerising partner | ALK: ? LTK: ? |
Pathway activated | ALK: Ras/MAPK, Rap1, PI3-K/TOR, ERK5, PLCγ, STATs, Jun LTK: Ras/MAPK, PI3-K/TOR, PLCγ |
Tissues expressed | ALK: central and peripheral nervous systems among other tissues LTK: pre-B and B lymphocytes and in the adult brain, as well as in placenta |
Human diseases | ALK: different types of cancer |
Knockout mouse phenotype | Both single and double knockouts are viable and fertile ALK: enhanced spatial memory and enhanced cognitive performance, effects on neurogenesis LTK: reduced sensimotor function ALK/LTK: reduced neurogenesis when compared with ALK KO |
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Palmer, R.H., Hallberg, B. (2015). The ALK Receptor Family. In: Wheeler, D., Yarden, Y. (eds) Receptor Tyrosine Kinases: Family and Subfamilies. Springer, Cham. https://doi.org/10.1007/978-3-319-11888-8_1
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