A role for the tyrosine kinase ACK1 in neurotrophin signaling and neuronal extension and branching

Anna La Torre Vila, M. Del Mar Masdeu, T. Cotrufo, R. S. Moubarak, J. A. Del Río, J. X. Comella, E. Soriano, J. M. Ureña

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Neurotrophins are involved in many crucial cellular functions, including neurite outgrowth, synapse formation, and plasticity. Although these events have long been known, the molecular determinants underlying neuritogenesis have not been fully characterized. Ack1 (activated Cdc42-associated tyrosine kinase) is a non-receptor tyrosine kinase that is highly expressed in the brain. Here, we demonstrate that Ack1 is a molecular constituent of neurotrophin signaling cascades in neurons and PC12 cells. We report that Ack1 interacts with Trk receptors and becomes tyrosine phosphorylated and its kinase activity is increased in response to neurotrophins. Moreover, our data indicate that Ack1 acts upstream of the Akt and MAPK pathways. We show that Ack1 overexpression induces neuritic outgrowth and promotes branching in neurotrophin-treated neuronal cells, whereas the expression of Ack1 dominant negatives or short-hairpin RNAs counteract neurotrophin-stimulated differentiation. Our results identify Ack1 as a novel regulator of neurotrophin-mediated events in primary neurons and in PC12 cells.

Original languageEnglish (US)
Article numbere602
JournalCell Death and Disease
Volume4
Issue number6
StatePublished - Jun 2013
Externally publishedYes

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Keywords

  • axonal
  • branching
  • dendritic
  • neurotrophins
  • tyrosine kinase

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

La Torre Vila, A., Del Mar Masdeu, M., Cotrufo, T., Moubarak, R. S., Del Río, J. A., Comella, J. X., Soriano, E., & Ureña, J. M. (2013). A role for the tyrosine kinase ACK1 in neurotrophin signaling and neuronal extension and branching. Cell Death and Disease, 4(6), [e602].