TrkC isoforms with inserts in the kinase domain show impaired signaling responses

Pantelis Tsoulfas, Robert M. Stephens, David R. Kaplan, Luis F. Parada

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The genetic locus for the TrkC/neurotrophin 3 (NT-3) receptor tyrosine kinase encodes multiple isoforms including receptors with inserts in the catalytic domain. This study examines the signaling capabilities of TrkC and related kinase insert isoforms TrkC14 and TrkC25. We show that in PC12 cells expressing both TrkC and TrkA/nerve growth factor (NGF) receptors, different morphological changes occur upon addition of NGF or NT-3. NT-3-treated cells exhibit longer neurites and larger cell bodies as compared to NGF-treated cells. Both TrkC and TrkA mediate qualitatively similar increases in the tyrosine phosphorylation of phospholipase C (PLC)-γ1, Shc, SNT, and MAPK and the transcription of the c-fos, c-jun, NGFI-A, and NGFI-B immediate early genes. However, the TrkC kinase insert forms fail to stimulate these events. Furthermore, TrkC14 and TrkC25 have only a low intrinsic tyrosine kinase activity, and insertion of the TrkC14 kinase insert into TrkA at an equivalent position results in a dramatic reduction of the kinase activity and signaling capabilities of TrkA. The TrkC14 and -25 isoforms may fail to transmit signals due to their low intrinsic kinase activity and failure to activate and/or tyrosine phosphorylate targets shown to be involved in neurotrophin signal transduction pathways.

Original languageEnglish
Pages (from-to)5691-5697
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number10
DOIs
StatePublished - Mar 8 1996
Externally publishedYes

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Protein Isoforms
Phosphotransferases
Cells
Neurotrophin 3
Nerve Growth Factor
Protein-Tyrosine Kinases
Tyrosine
trkC Receptor
Nerve Growth Factor Receptors
Signal transduction
Phosphorylation
Immediate-Early Genes
Genetic Loci
PC12 Cells
Nerve Growth Factors
Type C Phospholipases
Neurites
Transcription
Signal Transduction
Catalytic Domain

ASJC Scopus subject areas

  • Biochemistry

Cite this

TrkC isoforms with inserts in the kinase domain show impaired signaling responses. / Tsoulfas, Pantelis; Stephens, Robert M.; Kaplan, David R.; Parada, Luis F.

In: Journal of Biological Chemistry, Vol. 271, No. 10, 08.03.1996, p. 5691-5697.

Research output: Contribution to journalArticle

Tsoulfas, Pantelis ; Stephens, Robert M. ; Kaplan, David R. ; Parada, Luis F. / TrkC isoforms with inserts in the kinase domain show impaired signaling responses. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 10. pp. 5691-5697.
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