Expression of a chimeric CSF1R-LTK mediates ligand-dependent neurite outgrowth.
In an earlier screening, we identified several genes for kinases that might control the extension of neurites. One of these genes encoded a leukocyte tyrosine kinase (LTK), which is a receptor tyrosine kinase whose ligands remain to be identified. To examine the possible role of this LTK in neurite outgrowth, we constructed a chimeric receptor, in which the extracellular domain of the receptor for colony-stimulating factor-1 was fused to the cytoplasmic domain of LTK, which allowed the selective activation of LTK by colony-stimulating factor-1. Our studies using this chimeric receptor suggest that activation of the tyrosine kinase activity of LTK is sufficient to promote neurite outgrowth through pathways that include reactions catalyzed by phosphatidylinositol 3-kinase and MAPK.
Yamada
Shigeru
S
Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology, Kohtoh-ku, Tokyo, Japan.
Nomura
Takashi
T
Takano
Kota
K
Fujita
Satoshi
S
Miyake
Masato
M
Miyake
Jun
J
D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014162:Transfection
D011993:Recombinant Fusion Proteins; D016173:Macrophage Colony-Stimulating Factor; C489300:LTK protein, human; D020794:Receptor Protein-Tyrosine Kinases