Involvement of map kinase in the cyclic amp induction of myelin basic protein gene expression

Robert Clark, Mitchell Stewart, W. Keith Miskimins, Robin Miskimins

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The production of myelin, a multilamellar structure surrounding axons and allowing rapid conductance of nerve impulses, is performed by specialized cells in the central and peripheral nervous systems. This function is performed by oligodendrocytes in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS). The developmental program followed by oligodendrocyte and Schwann cell progenitors leading to the production of myelin is clearly affected by different hormones and growth factors. While not all of these have been defined, it is clear that increased cyclic AMP (cAMP) levels accelerate the expression of a differentiated phenotype. This includes increased expression of myelin components, such as myelin basic protein (MBP). Previous work has shown that this increase in MBP in response to elevated cAMP levels occurs by increased transcription of the MBP gene. It is currently unknown what the endogenous substance is that increases cAMP levels during differentiation of myelin producing cells. Additionally, the signalling pathway(s) that lead to differentiation and increased expression of the genes coding for myelin products in the CNS and PNS remains to be elucidated.It has recently been demonstrated that cAMP can modulate the neuronal differentiation of PC12 cells via its activation of the MAP kinase (mitogen-activated protein kinase) cascade. The MAP kinases can be grouped into three families that include the extracellular signal-regulated kinase (ERKs), Jun N-terminal kinase (JNKs)\stress-activated protein kinase (SAPKs) and p38. Activation of many MAP kinases is a rapid cellular response to both growth and differentiation factors. MAP kinases function within a kinase cascade and can be activated by phosphorylation on Thr and Tyr residues by dual specificity enzymes such as MEK (MAP kinase kinase). MEK, in turn, can be activated by at least two different pathways. Since MAP kinases have an important role in intracellular signalling in response to differentiation stimuli we have investigated whether or not MAP kinases play a role in the differentiation pathway activated by increased intracellular cAMP. Utilizing a cell line, D6P2T, that is capable of responding to increases in cAMP levels with expression of the MBP gene, similar to the response of oligodendrocyte and Schwann cells, we demonstrate a role for MAP kinase in the signal transduction cascade initiated by cAMP leading to increased MBP gene expression. Copyright (C) 1997 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)323-331
Number of pages9
JournalInternational Journal of Developmental Neuroscience
Volume16
Issue number5
DOIs
StatePublished - Aug 1 1998

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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