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
02/26/1999Pubmed ID
10037749DOI
10.1074/jbc.274.10.6553Scopus ID
2-s2.0-0033525882 46 CitationsAbstract
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 MFAuthor
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3T3 CellsAnimals
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
