The c-Fes protein-tyrosine kinase accelerates NGF-induced differentiation of PC12 cells through a PI3K-dependent mechanism

Annemarie Shibata, Charles E. Laurent, Thomas E. Smithgall

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The c-fes protooncogene encodes a non-receptor protein-tyrosine kinase (Fes) that has been implicated in the differentiation of myeloid haematopoietic cells. Fes is also expressed in several neuronal cell types and the vascular endothelium, suggestive of a more general function in development. To examine the role of Fes in neuronal differentiation, we investigated the effect of Fes expression on process outgrowth in PC12 cells following stimulation with nerve growth factor (NGF). PC12 cells expressing wild-type and activated mutants of Fes extended processes faster and of greater length than control cells. In contrast, expression of kinase-inactive Fes was without effect, indicating that cooperation with NGF requires Fes kinase activity. Short-term treatment of PC12-Fes cells with NGF enhanced tyrosine phosphorylation of Fes, suggesting upstream regulation by the NGF receptor. Fes-mediated acceleration of neurite outgrowth was blocked by wortmannin and LY294002, implicating phosphatidylinositol 3-kinase (PI3K) activation in the Fes-induced response. In contrast, the MEK inhibitor PD98059 was without effect, suggesting that the Ras-Erk pathway is not involved. These data provide the first evidence that Fes may contribute to morphological differentiation of neuronal cells by enhancing NGF signalling through the PI3K pathway.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalCellular Signalling
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Proto-Oncogene Proteins c-fes
Phosphatidylinositol 3-Kinase
PC12 Cells
Nerve Growth Factor
Protein-Tyrosine Kinases
Phosphotransferases
Nerve Growth Factor Receptor
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Mitogen-Activated Protein Kinase Kinases
Vascular Endothelium
Myeloid Cells
Tyrosine
Cell Differentiation
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

The c-Fes protein-tyrosine kinase accelerates NGF-induced differentiation of PC12 cells through a PI3K-dependent mechanism. / Shibata, Annemarie; Laurent, Charles E.; Smithgall, Thomas E.

In: Cellular Signalling, Vol. 15, No. 3, 01.03.2003, p. 279-288.

Research output: Contribution to journalArticle

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