SCF and G-CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways
Publicated to:BLOOD. 96 (10): 3422-3430 - 2000-11-15 96(10), DOI: 10.1182/blood.v96.10.3422
Authors: Duarte R.F., Frank D.A.
Affiliations
Abstract
Stem cell factor (SCF) is a potent costimulatory molecule for many cytokines. Its synergy with granulocyte colony-stimulating factor (G-CSF) results in important biologic and clinical effects, although the mechanism by which this occurs remains poorly understood. To investigate this interaction, this study used a retroviral vector to transduce the G-CSF receptor into MO7e cells, which are known to express the SCF receptor. The transduced G-CSF receptor is functionally active, and the resultant MO7e-G cells recapitulate the proliferative synergy between SCF and G-CSF. When treated with both cytokines, a marked shortening of the G(0)/G(1) phase of the cell cycle occurs, associated with a suppression of the cyclin-dependent kinase inhibitor p27(kip-1). In addition, SCF and G-CSF induce the synergistic activation of c-fos, a proto-oncogene involved in propagation of mitogenic signals in hematopoietic cells. G-CSF, but not SCF, induces the tyrosine phosphorylation of STAT1 and STAT3, transcription factors that can mediate the induction of c-fos. However, SCF induces phosphorylation of STAT3 on serine727 (ser727), which is necessary for maximal STAT transcriptional activity, and the combination of SCF and G-CSF leads to complete STAT3 phosphorylation on ser727. The pathways by which SCF and G-CSF lead to serine phosphorylation of STAT3 are distinct and are partially dependent on phosphatidylinositol-3 kinase and ERKs, pathways that are also necessary for the synergistic effects of SCF and G-CSF on proliferation and c-fos induction. Thus, MO7e-G cells provide a powerful system in which the molecular basis of the synergy between SCF and G-CSF can be dissected.
Keywords
Quality index
Bibliometric impact. Analysis of the contribution and dissemination channel
The work has been published in the journal BLOOD due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2000, it was in position 3/60, thus managing to position itself as a Q1 (Primer Cuartil), in the category Hematology.
From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.46, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Aug 2025)
Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-04, the following number of citations:
- WoS: 48
- Scopus: 52
Impact and social visibility
Leadership analysis of institutional authors
This work has been carried out with international collaboration, specifically with researchers from: United States of America.
There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (DUARTE PALOMINO, RAFAEL FRANCISCO) .