Differential Patterns of ERK and STAT3 Phosphorylation after Sciatic Nerve Transection in the Rat

doi:10.1006/exnr.2000.7508

Experimental Neurology

Volume 166, Issue 2, December 2000, Pages 392-402

https://doi.org/10.1006/exnr.2000.7508 Get rights and content

Abstract

Peripheral nerve injury induces a specific pattern of expression of growth factors and cytokines, which regulate injury responses and regeneration. Distinct classes of growth factors and cytokines signal through specific intracellular phosphorylation cascades. For example, the ERK phosphorylation cascade mediates signaling through transmembrane tyrosine kinase receptors and the JAK/STAT cascade mediates signaling through the GP130 receptor complex. We tested whether specific phosphorylation patterns of ERK and STAT3 result from nerve injury and whether such phosphorylation correlates with the expression of specific growth factors and cytokines. At sites adjacent to a nerve transection, we observed that ERK phosphorylation peaked early, persisted throughout 16 days, and was equally intense at proximal and distal sites. In contrast, STAT3 phosphorylation peaked later than ERK but did not persist as long and was stronger in the proximal than in the distal segment adjacent to the injury. In addition, in distal segments further away from the injury site, ERK became phosphorylated with a delayed time course, while STAT3 remained unphosphorylated. These patterns of phosphorylation correlated well with the expression of neurotrophin and interleukin-6 mRNAs in the distal stump. In addition, we found that the pattern of SAPK phosphorylation is similar to the pattern observed for STAT3, while the pattern of macrophage infiltration into the transected nerve was distinct from all the phosphorylation patterns observed. Together, these observations suggest that ERK activation is important in the establishment of a regeneration-promoting extracellular environment in the far distal stump of transected nerves and that STAT3 activation is important in the control of cellular responses close to the site of injury.

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Regular ArticleDifferential Patterns of ERK and STAT3 Phosphorylation after Sciatic Nerve Transection in the Rat

Abstract

Exp. Neurol.

J. Neuroimmunol.

Neuron

Neuron

Cell

Brain Res.

Cell

Cell Signal

J. Neuroimmunol.

Exp. Neurol.

J. Biol. Chem.

Interleukin-6 production by Schwann cells and induction in sciatic nerve injury

J. Neurochem.

Expression of neuregulins and their putative receptors, erbb2 and erbb3, is induced during wallerian degeneration

J. Neurosci.

Neurturin shares receptors and signal transduction pathways with glial cell line-derived neurotrophic factor in sympathetic neurons

Proc. Natl. Acad. Sci. USA

Fibroblast growth factors stimulate protein tyrosine phosphorylation and mitogen-activated protein kinase activity in primary cultures of hippocampal neurons

J. Neurochem.

Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins

Science

Schwann cell proliferation

Acidic and basic fibroblast growth factors in the nervous system: Distribution and differential alteration of levels after injury of central versus peripheral nerve

J. Neurosci.

Peripheral nerve regeneration

Annu. Rev. Neurosci.

Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve

J. Cell Biol.

Regular Article
Differential Patterns of ERK and STAT3 Phosphorylation after Sciatic Nerve Transection in the Rat