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Protein Kinase C Activity is Necessary for Estrogen-Induced Erk Phosphorylation in Neocortical Explants

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Abstract

Our laboratory showed previously that estrogen activates ERK in neocortical cultures. To further elucidate the precise signaling sequelae that lead to estrogen-induced ERK activity, we evaluated the involvement of protein kinase C (PKC). We found that neocortical explants expressed primarily PKC gamma and PKC epsilon. Consistent with the involvement of PKC in mediating estrogen-induced ERK phosphorylation, we found that estrogen treatment induced translocation of these PKC isoforms to the plasma membrane. Importantly, inhibition of these isoforms abolished the ability of estrogen to phosphorylate ERK. While direct activation of PKC mimicked the effect of estrogen on ERK, both in pattern of activation and resulting intraneuronal distribution of ERK, PKC-induced ERK phosphorylation required the activity of MEK but not B-Raf. Collectively, these data suggest a critical role for PKC in mediating estrogen induction of ERK activation in the developing brain via a MEK-dependent but B-Raf-independent pathway.

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Abbreviations

BDNF:

brain-derived neurotrophic factor

Bim:

bisindolylmaleimide-I HCl

B-Raf:

the B isoform of the serine / threonine kinase named Raf

CHX:

cycloheximide

c-Src:

a protein tyrosine kinase

E2:

estradiol

ERK1/2:

isoforms 1 and 2 of extracellular signal-regulated kinase

H-Ras:

a 21 kDa G-protein

MAPK:

mitogen-activated protein kinase

MEK2:

isoform-2 of the dual-specificity kinase named MEK, abbreviated from Mitogen-activated/extracellular signal-regulated kinase Kinase

NGF:

nerve growth factor

PC12:

a rat pheochromocytoma cell line

p-ERK1/2:

the phosphorylated forms of ERK1/2

PKC:

protein kinase C

PLC:

phospholipase C

TPA:

tetradecanoyl phorbol acetate

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Authors and Affiliations

  1. Departments of Anatomy & Cell Biology, Columbia University College of Physicians & Surgeons, 650 West 168th Street, Black Building 1615, New York, NY, 10032, USA

    György Sétáló Jr., Meharvan Singh, Imam S. Nethrapalli & C. Dominique Toran-Allerand

  2. Neurology, and Centers for Neurobiology & Behavior and Reproductive Sciences, Columbia University College of Physicians & Surgeons, New York, NY, 10032, USA

    György Sétáló Jr., Meharvan Singh, Imam S. Nethrapalli & C. Dominique Toran-Allerand

  3. Department of Medical Biology, Faculty of Medicine, Pécs University, H-7643, Pécs, Hungary

    György Sétáló Jr.

  4. Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA

    Meharvan Singh

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  1. György Sétáló Jr.
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  4. C. Dominique Toran-Allerand
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Correspondence to C. Dominique Toran-Allerand.

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Sétáló, G., Singh, M., Nethrapalli, I.S. et al. Protein Kinase C Activity is Necessary for Estrogen-Induced Erk Phosphorylation in Neocortical Explants. Neurochem Res 30, 779–790 (2005). https://doi.org/10.1007/s11064-005-6871-y

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