PMID- 12032835
OWN - NLM
STAT- MEDLINE
DCOM- 20020614
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 21
IP  - 23
DP  - 2002 May 23
TI  - Opposite effects of different doses of MCSF on ERK phosphorylation and cell 
      proliferation in macrophages.
PG  - 3670-6
AB  - We had previously shown that murine macrophages expressing v-Fes, the 
      oncogenically activated counterpart of the c-Fes cytoplasmic tyrosine kinase, 
      proliferate independently of Macrophage Colony-Stimulating Factor (MCSF) and that 
      the Extracellular signal-Regulated Kinase (ERK) pathway mediates the mitogenic 
      effect of v-Fes. In this study, the response of c-fes- and v-fes-overexpressing 
      cells to MCSF was investigated. A critical modulation of the activation of 
      Mitogen-activated ERK Kinase (MEK) and ERK based on the MCSF dose was 
      characterized. ERK activation was increased by MCSF doses capable to elicit a 
      mitogenic response (2-5 U/ml). On the contrary, MCSF doses as low as 0.05 U/ml 
      markedly reduced ERK phosphorylation and nuclear content and moderately but 
      significantly reduced cell proliferation. The reduction of MEK and ERK 
      phosphorylation was very rapid, suggesting the involvement of cytosolic 
      phosphatases. Among these, phospho-tyrosine protein phosphatases and 
      phosphoserine/threonine protein phosphatase-2A were found involved. These 
      findings represent the first observation that different doses of the same growth 
      factor, MCSF in particular, can exert opposite effects on cell proliferation by 
      switching on or off ERK signaling.
FAU - Rovida, Elisabetta
AU  - Rovida E
AD  - Department of Experimental Pathology and Oncology, Universita degli Studi di 
      Firenze, Florence, Italy.
FAU - Baccarini, Manvela
AU  - Baccarini M
FAU - Olivotto, Massimo
AU  - Olivotto M
FAU - Dello Sbarba, Persio
AU  - Dello Sbarba P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Arsenicals)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - 57F9KU116M (benzenearsonic acid)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (FES protein, human)
RN  - EC 2.7.10.2 (Fes protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fes)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Arsenicals/pharmacology
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Humans
MH  - MAP Kinase Kinase 1
MH  - Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Macrophages/*cytology/*drug effects/enzymology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Okadaic Acid/pharmacology
MH  - Phosphorylation/drug effects
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - *Protein-Tyrosine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-fes
MH  - Signal Transduction/drug effects
MH  - Time Factors
EDAT- 2002/05/29 10:00
MHDA- 2002/06/18 10:01
CRDT- 2002/05/29 10:00
PHST- 2001/07/02 00:00 [received]
PHST- 2002/02/08 00:00 [revised]
PHST- 2002/03/22 00:00 [accepted]
PHST- 2002/05/29 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/05/29 10:00 [entrez]
AID - 10.1038/sj.onc.1205409 [doi]
PST - ppublish
SO  - Oncogene. 2002 May 23;21(23):3670-6. doi: 10.1038/sj.onc.1205409.