Signaling pathways for PC12 cell differentiation: making the right connections.
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 --> mitogen-activated protein kinase kinase (MEK) --> 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.
Vaudry
D
D
Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD 20892, USA.
Stork
P J S
PJ
Lazarovici
P
P
Eiden
L E
LE
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D016716:PC12 Cells / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D020218:Response Elements; D014158:Transcription, Genetic
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D000242:Cyclic AMP; D020917:Receptor, trkA; D020928:Mitogen-Activated Protein Kinases