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Updated: Jul 22, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Specific TrkA survival signals interfere with different apoptotic pathways

E Ulrich1, A Duwel, A Kauffmann-Zeh

  • 1Imperial Cancer Research Fund Laboratories, London, UK.

Oncogene
|March 4, 1998
PubMed

Insights

Nerve growth factor receptor TrkA delays apoptosis by activating distinct pathways. The Akt/PKB pathway is crucial for U.V.-induced apoptosis, while c-Myc-induced apoptosis involves a novel, Akt/PKB-independent pathway.

Area of Science:

  • Cell biology
  • Molecular biology
  • Signal transduction

Background:

  • Tyrosine kinase receptors, like TrkA, are vital for cell survival by balancing cell viability and apoptosis.
  • Understanding the specific domains and pathways involved in TrkA-mediated survival signaling is crucial for deciphering cellular fate decisions.

Purpose of the Study:

  • To investigate the role of specific TrkA receptor domains in mediating survival signaling against different apoptotic stimuli.
  • To elucidate the downstream signaling pathways, including Akt/PKB and MAPK, activated by TrkA in response to various apoptotic triggers.

Main Methods:

  • Expression of wild-type (wt) and mutant TrkA receptors (Y490F, Y785F, YY490/785FF) in Rat-1/MycER fibroblasts.
  • Assessment of TrkA's ability to delay apoptosis induced by c-Myc, U.V. irradiation, and Cycloheximide.
  • Analysis of downstream signaling pathway activation (MAPK Erk2, Akt/PKB) and inhibition using specific kinase inhibitors (LY294002, Wortmannin).

Main Results:

  • wt-TrkA delays apoptosis induced by c-Myc, U.V., and Cycloheximide, activating Erk2 and Akt/PKB.
  • TrkA Y490F mutant delays c-Myc-induced apoptosis but not U.V.-induced apoptosis, and does not activate Akt/PKB.
  • TrkA Y785F mutant protects against both c-Myc and U.V.-induced apoptosis, while the double mutant YY490/785FF loses this protective ability.
  • PI3-kinase inhibitors block U.V.-induced survival but not c-Myc-induced survival mediated by TrkA.
  • U.V.-induced apoptosis relies on the Akt/PKB pathway, whereas c-Myc-induced apoptosis is inhibited via a novel, Akt/PKB-independent pathway.

Conclusions:

  • TrkA employs distinct signaling pathways to counteract specific apoptotic stimuli.
  • The Akt/PKB pathway is essential for TrkA-mediated survival against U.V. damage.
  • A novel, Akt/PKB-independent pathway activated by TrkA contributes to survival against c-Myc-induced apoptosis.
  • These findings highlight the adaptability of TrkA signaling in regulating cell survival through multiple mechanisms.

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