ErbB-4 activation inhibits apoptosis in PC12 cells

S. Erlich, Y. Goldshmit, Z. Lupowitz, R. Pinkas-Kramarski

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Neuregulins, a large family of polypeptide growth factors, exert various distinctive effects in the nervous system. Neuregulins and their receptors are widely expressed in neurons implying important roles in neuronal cell functions. Recently, we have shown that ErbB-4 receptors expressed in PC12 cells mediate neuregulin-induced differentiation. In the present study we demonstrate that in the PC12-ErbB-4 cells, neuregulin rescues cells from apoptosis induced by serum deprivation or tumor necrosis factor (TNF)α treatment. The neuregulin-induced survival is comparable to the effect mediated by the neurotrophic factor nerve growth factor (NGF). Both neuregulin and NGF protect cells from apoptosis induced by serum deprivation and TNFα treatment. Moreover, neuregulin like NGF induces the survival of neuronal differentiated PC12-ErbB-4 cells. The survival effect of neuregulin is probably mediated by the phosphoinositide 3-kinase (PI3K) and protein kinase B/Akt signaling pathways. Neuregulin induces the activation of PI3K and prolonged activation of protein kinase B/Akt. In addition, inhibition of the PI3K activity prevented the neuregulin-induced survival effect. Taken together, these results indicate that survival induced by neuregulin in PC12-ErbB-4 cells requires PI3K signaling networks.

Original languageEnglish
Pages (from-to)353-362
Number of pages10
JournalNeuroscience
Volume107
Issue number2
DOIs
StatePublished - 16 Nov 2001

Funding

FundersFunder number
Charles E. Kaufman Foundation1190, 7-2001 No. 34-01
National Institute for Psychobiology in Israel, Hebrew University of Jerusalem

    Keywords

    • Epidermal growth factor
    • ErbB/HER family
    • Neu differentiation factor
    • Neuregulin
    • Signal transduction
    • Tyrosine kinase

    Fingerprint

    Dive into the research topics of 'ErbB-4 activation inhibits apoptosis in PC12 cells'. Together they form a unique fingerprint.

    Cite this