Related Experiment Video

Updated: Jul 30, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

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.

Molecular and Cellular Biology
|July 13, 2000
PubMed

Insights

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

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing09:02

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing

Published on: June 9, 2017

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-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 Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
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 Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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 Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...