Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1998-5-22
pubmed:abstractText
The differentiation of muscle cells is controlled by the MyoD family of transcription factors. This family is regulated by extracellular growth factors that transmit largely unknown signals into the cells. Here we show that the activity of extracellular signal-regulated protein kinase (ERK), a kinase that is part of the mitogen-activated protein kinase (MAPK) cascade, is low in myoblasts and is induced with the onset of terminal differentiation of C2 cells. ERK activity is also induced in fibroblasts that were modified to express MyoD, but not in the parental fibroblast cells. Thus, ERK induction is an intrinsic property of muscle cells. A specific MAPK kinase inhibitor (PD098059) that was added to C2 cells partially inhibited the fusion of myoblasts to multinucleated myotubes without affecting the expression of muscle-specific markers. This inhibitor blocked the induction of MyoD expression that normally takes place during terminal differentiation. Two lines of evidence suggest that the MAPK cascade induces the activity of MyoD: 1) the expression of constitutively activated forms of MEK1 or Raf1 enhanced the transcriptional activity of MyoD in 10T1/2 fibroblasts; and 2) the addition of PD098059 to fibroblast cells expressing a conditional MyoD-estrogen fusion protein significantly inhibited the expression of MyoD-responsive genes. Our results indicate that the MAPK pathway is activated in differentiating muscle cells and that it positively regulates the expression and activity of MyoD protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10436-44
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Mitogen-activated protein kinase pathway is involved in the differentiation of muscle cells.
pubmed:affiliation
Department of Biochemistry, Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't