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Science 31 May 2002:
Vol. 296. no. 5573, pp. 1648 - 1649
DOI: 10.1126/science.1071552
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Signaling Pathways for PC12 Cell Differentiation: Making the Right Connections

D. Vaudry,1 P. J. S. Stork,2 P. Lazarovici,3 L. E. Eiden1*

A key issue in signal transduction is how signaling pathways common to many systems--so-called canonical signaling cassettes--integrate signals from molecules having a wide spectrum of activities, such as hormones and neurotrophins, to deliver distinct biological outcomes. The neuroendocrine cell line PC12, derived from rat pheochromocytoma, provides an example of how one canonical signaling cassette--the Raf rightarrow  mitogen-activated protein kinase kinase (MEK) rightarrow  extracellular signal-regulated kinase (ERK) pathway--can promote distinct outcomes, which in this case include neuritogenesis, gene induction, and proliferation. Two growth hormones, epidermal growth factor (EGF) and nerve growth factor (NGF), use the same pathway to cause PC12 proliferation and differentiation, respectively. In addition, pituitary adenylate cyclase-activating polypeptide (PACAP), a neurotransmitter that also causes differentiation, uses the same canonical cassette as NGF but in a different way. The Connections Map for PC12 Cell Differentiation brings into focus the complex array of specific cellular responses that rely on canonical signal transduction systems.

1 Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD 20892, USA.
2 Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA.
3 Department of Pharmacology, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
*   To whom correspondence should be addressed. E-mail: eiden{at}codon.nih.gov

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