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Expression of c-Myc in response to colony-stimulating factor-1 requires mitogen-activated protein kinase kinase-1. J Biol Chem 1999 Mar 05;274(10):6553-8

Date

02/26/1999

Pubmed ID

10037749

DOI

10.1074/jbc.274.10.6553

Scopus ID

2-s2.0-0033525882   46 Citations

Abstract

The mitogen-inducible gene c-myc is a key regulator of cell proliferation and transformation. Yet, the signaling pathway(s) that regulate its expression have remained largely unresolved. Using the mitogen-activated protein kinase kinase (MEK1/2) inhibitor PD98059 and dominant negative forms of Ras (N17) and ERK1 (K71R), we found that activation of Ras and extracellular signal-regulated kinase (ERK) is necessary for colony-stimulating factor-1 (CSF-1)-mediated c-Myc expression and DNA synthetic (S) phase entry. Quiescent NIH-3T3 cells expressing a partially defective CSF-1 receptor, CSF-1R (Y809F), exhibited impaired ERK1 activation and c-Myc expression and failed to enter the S phase of the cell division cycle in response to CSF-1 stimulation. Ectopic expression of a constitutively active form of MEK1 in cells expressing CSF-1R (Y809F) rescued c-Myc expression and S phase entry, but only in the presence of CSF-1-induced cooperating signals. Therefore, MEK1 participates in an obligate signaling pathway linking CSF-1R to c-Myc expression, but other signals from CSF-1R must cooperate with the MEK/ERK pathway to induce c-Myc expression and S phase entry in response to CSF-1 stimulation.

Author List

Cheng M, Wang D, Roussel MF

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

3T3 Cells
Animals
Enzyme Activation
Gene Expression Regulation
Genes, myc
MAP Kinase Kinase 1
Macrophage Colony-Stimulating Factor
Mice
Mitogen-Activated Protein Kinase Kinases
Protein-Serine-Threonine Kinases
Protein-Tyrosine Kinases
Signal Transduction
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5