| Autor: |
Sarbassov DD; Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences and The Geriatric Research, Education, and Clinical Center, McClellan Veterans Hospital, Little Rock 72205, USA., Peterson CA |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular endocrinology (Baltimore, Md.) [Mol Endocrinol] 1998 Dec; Vol. 12 (12), pp. 1870-8. |
| DOI: |
10.1210/mend.12.12.0205 |
| Abstrakt: |
Activation of the insulin-like growth factor (IGF) autocrine loop is required for myogenic differentiation and results in sustained activation of extracellular signal-regulated kinases-1 and -2 (ERK-1 and -2). We show here that insulin receptor substrate-1 (IRS-1) phosphorylation on tyrosine and serine residues and association with phosphatidylinositol 3-kinase (PI 3-kinase) are also associated with IGF-dependent myogenic differentiation. Down-regulation of IRS-1 is linked to its serine phosphorylation dependent on PI 3-kinase activity and appears required for differentiation to occur, as IRS-1 is not modified and continues to accumulate in a nondifferentiating myoblast cell line. Furthermore, inhibition of PI 3-kinase activity with LY294002 blocks differentiation, as demonstrated by inhibition of myogenin and myosin heavy chain expression and ERK activation. Blocking the Raf/MEK/ERK cascade with PD98059 does not block myogenic differentiation; however, myotubes do not survive. Thus, PI 3-kinase, in association with IRS-1, is involved in an ERK-independent signaling pathway in myoblasts required for IGF-dependent myogenic differentiation and in inducing sustained activation of ERKs necessary for later stages of differentiation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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