Related Experiment Video
Updated: Jul 30, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
Different protein kinase C isoforms determine growth factor specificity in neuronal cells
K C Corbit1, J W Soh, K Yoshida
1Neurobiology, Pharmacology and Physiology Department and Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.
Different protein kinase C (PKC) isoforms, PKCzeta and PKCdelta, dictate distinct cellular responses to growth factors like EGF and FGF by modulating common signaling pathways, revealing a mechanism for biological diversity.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Growth factors trigger diverse cellular outcomes via common signaling pathways.
- Mechanisms differentiating these outcomes remain unclear.
- Previous work showed distinct protein kinase C (PKC) dependency for mitogen-activated protein (MAP) kinase activation by different growth factors.
Purpose of the Study:
- Elucidate the specific signaling pathways utilized by epidermal growth factor (EGF) and fibroblast growth factor (FGF).
- Investigate the role of different protein kinase C (PKC) isoforms in mediating distinct cellular responses to growth factors.
- Determine how growth factor signaling specificity is achieved within neural cells.
Main Methods:
- Utilized rat hippocampal (H19-7) and pheochromocytoma (PC12) cell lines.
- Employed inhibitors to block specific protein kinase C (PKC) isoforms (PKCzeta, PKCdelta).
- Monitored mitogen-activated protein (MAP) kinase activation, DNA synthesis (bromodeoxyuridine incorporation), and upstream signaling intermediates (phosphatidylinositol 3-kinase, PDK1, MEK, Raf-1).
Main Results:
- Epidermal growth factor (EGF) activates MAP kinase via a PKCzeta-dependent pathway involving phosphatidylinositol 3-kinase and PDK1.
- PKCzeta acts upstream of MEK and potentiates Raf-1 activation by EGF.
- Inhibition of PKCzeta blocks EGF-induced DNA synthesis.
- PKCzeta and PKCdelta inhibitors differentially suppress MAP kinase activation by EGF and FGF, respectively, in primary neural cells.
Conclusions:
- Different protein kinase C (PKC) isoforms (PKCzeta and PKCdelta) confer signaling specificity for distinct growth factors (EGF and FGF).
- This isoform-specific activation provides a mechanism for generating biological diversity from common signaling intermediates.
- These findings are relevant to both immortalized and primary neural cells.
More Related Videos
09:02Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
Published on: June 9, 2017
09:32Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Related Concept Videos
Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade
MAPK Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway
Activation and Inactivation of G Proteins