Control of Myeloid-specific Integrin αMβ2 (CD11b/CD18) Expression by Cytokines Is Regulated by Stat3-dependent Activation of PU.1
Open accessAbstract
Granulocyte colony-stimulating factor (G-CSF) plays an essential role in regulating multiple aspects of hematopoiesis. To elucidate the role of G-CSF in controlling hematopoietic cell migration capabilities, we studied inducible expression of the myeloid-specific marker, integrin alpha(M)beta(2) (CD11b/CD18, Mac-1), in the myeloid cell line, 32D. We found that G-CSF stimulates the synthesis and cell surface expression of alpha(M) and beta(2) integrin subunits. Induction of both alpha(M) and beta(2) is dependent on Stat3, a major G-CSF-responsive signaling protein. However, the kinetics of expression suggested the involvement of an intermediate protein regulated by Stat3. Our results demonstrate that Stat3 signaling stimulates the expression of PU.1, a critical regulator of myelopoiesis. Furthermore, we show that PU.1 is an essential intermediate for the inducible expression of alpha(M)beta(2) integrin. Thus, Stat3 promotes alpha(M)beta(2) integrin expression through its activation of PU.1. These findings indicate that G-CSF-dependent Stat3 signals stimulate the changes in cell adhesion and migration capabilities that occur during myeloid cell development. These data also demonstrate a link between Stat3 and PU.1, suggesting that Stat3 may play an instructive role in hematopoiesis.
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Tcf4/E2-2 is transcriptionally upregulated by STAT3.
“Tcf4/E2-2, another transcriptional regulator of plasmacytoid DC development, is also transcriptionally upregulated by STAT3”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Panopoulos et al., 2002
The Discussion describes STAT3-dependent induction of PU.1 and the myeloid integrin αMβ2, not Tcf4/E2-2. Searches for Tcf4/E2-2 and plasmacytoid dendritic cells found no passage addressing whether STAT3 transcriptionally upregulates Tcf4/E2-2. Page numbers were unavailable in our copy. (LLM, conf=0.76)
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References 42 · Cited by 58
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- Authors
- Panopoulos, A. D., Bartos, D., Zhang, L., & Watowich, S. S.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Watowich, Stephanie S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 277
- Issue
- 21
- Pages
- 19001-19007
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2388249
- OpenAlex
- W2024814259
- Cited by
- 58
- References
- 42
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA077447, CA77447)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- Mac-1, CD11b/CD18, granulocyte colony-stimulating factor, STAT3 signaling, PU.1, myeloid cell migration, cell adhesion, myelopoiesis, cytokine regulation of gene expression, hematopoiesis
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Base Sequence, Bone Marrow, Cell Adhesion, Cell Line, DNA-Binding Proteins, Proto-Oncogene Proteins, Signal Transduction, Trans-Activators, Macrophage-1 Antigen, Granulocyte Colony-Stimulating Factor, Receptors, Granulocyte Colony-Stimulating Factor, DNA Primers, COS Cells, STAT3 Transcription Factor, Mice
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