STAT-3 Activation Is Required for Normal G-CSF-Dependent Proliferation and Granulocytic Differentiation

McLemore, Morgan L.; Grewal, Satkiran S.; Liu, Fulu; Archambault, Angela S.; Poursine-Laurent, Jennifer; Haug, Jeff; Link, Daniel C.

doi:10.1016/s1074-7613(01)00101-7

Cited by 182 publications

(169 citation statements)

References 47 publications

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…This result suggests a direct effect of IFN␥ in activating this signaling pathway that, in several in vitro studies, is shown to link cytokine signaling with cell proliferation. 30,31 Collectively, these data provide compelling evidence that IFN␥ signaling is required for an optimal oval cell response.…”

Section: Discussionmentioning

confidence: 95%

Differential lymphotoxin-? and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury

et al. 2005

View full text Add to dashboard Cite

The liver regenerates after acute injury via hepatocyte cell division; during chronic injury, when hepatocyte replication is impaired or blocked, liver progenitor oval cells mediate liver regeneration. If both regeneration options are blocked in animal models, then liver failure and death ensues. The mechanisms underlying oval cell induction, proliferation, and subsequent liver regeneration remain poorly characterized. In particular, cell-signaling pathways that distinguish the alternative pathways are unknown. This study shows that in a mouse model, hepatic expression of lymphotoxin-␤ (LT␤) and interferon gamma ( T he liver has the capacity to regenerate after acute injury by hepatocyte cell division. However, in circumstances where hepatocyte proliferation is attenuated or blocked, the liver is repopulated after induction, proliferation, and differentiation of the stem cell compartment, which includes oval cells. 1 These alternative methods of liver regeneration can be modeled in mice by partial hepatectomy (PHx) and by feeding them a choline-deficient, ethionine-supplemented (CDE) diet. Surgical resection of a portion of liver mimics acute injury, stimulating a replication response from residual healthy parenchymal cells, which undergo cell division to replace the lost liver mass. 1 The CDE diet damages the liver parenchyma and prevents hepatocyte division, leading to activation and rapid induction of large numbers of oval cells in mice. 2 The replication response after PHx involves a rapid and highly coordinated series of biochemical events resulting in hepatocytes undergoing a relatively synchronized progression through the cell cycle. Immediately after the insult, immediate early genes are activated by transcription factors such as nuclear factor kappa B, activating protein 1 (AP1), and STAT-3. The immediate early phase lasts approximately 4 hours in rodents and precedes the delayed early gene response, which renders the hepatocytes responsive to growth factors that drive the

show abstract

Section: Discussionmentioning

confidence: 95%

Differential lymphotoxin-? and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Although STAT3 has been linked to myeloid cell differentiation (17,51), STAT5 seems to be involved in G-CSF-dependent cell proliferation (18). Because we found a potent induction of SOCS-3 mRNA in U937 cells as well as in primary neutrophils upon G-CSF stimulation, we examined the impact of SOCS-3 on G-CSF-induced STAT DNA binding by means of a STAT-luciferase assay.…”

Section: Discussionmentioning

confidence: 99%

Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction

Hörtner

Nielsch

Mayr

et al. 2002

The Journal of Immunology

121

View full text Add to dashboard Cite

G-CSF is a polypeptide growth factor used in treatment following chemotherapy. G-CSF regulates granulopoiesis and acts on its target cells by inducing homodimerization of the G-CSFR, thereby activating intracellular signaling cascades. The G-CSFR encompasses four tyrosine motifs on its cytoplasmic tail that have been shown to recruit a number of regulatory proteins. Suppressor of cytokine signaling 3 (SOCS-3), also referred to as cytokine-inducible Src homolgy 2-containing protein 3, is a member of a recently discovered family of feedback inhibitors that have been shown to inhibit the Janus kinase/STAT pathway. In this study, we demonstrate that human SOCS-3 is rapidly induced by G-CSF in polymorphonuclear neutrophils as well as in the myeloid precursor cell line U937 and that SOCS-3 negatively regulates G-CSFR-mediated STAT activation. Most importantly, we show that SOCS-3 is recruited to the G-CSFR in a phosphorylation-dependent manner and we identify phosphotyrosine (pY)729 as the major recruitment site for SOCS-3. Furthermore, we demonstrate that SOCS-3 directly binds to this pY motif. Surface plasmon resonance analysis reveals a dissociation constant (KD) for this interaction of around 2.8 μM. These findings strongly suggest that the recruitment of SOCS-3 to pY729 is important for the modulation of G-CSFR-mediated signal transduction by SOCS-3.

show abstract

“…In addition, Stat3C expression did not abrogate growth factor dependence and had no effect on IL-3-dependent growth, similar to what was previously reported for bone marrow cells. 25 A 'stabilized' PI3-kinase expressed in DKI cells is substantially able to restore CSF-1-dependent mitogenesis…”

Section: Csf-1-dependent Mitogenesis Requires Both Erk and Pi3-kinasementioning

confidence: 99%

Colony-stimulating factor-1 requires PI3-kinase-mediated metabolism for proliferation and survival in myeloid cells

Lee

States

2006

Cell Death Differ

View full text Add to dashboard Cite

Colony-stimulating factor-1 (CSF-1) is essential for macrophage growth, differentiation and survival. Myeloid cells expressing a CSF-1 receptor mutant (DKI) show markedly impaired CSF-1-mediated proliferation and survival, accompanied by absent signal transducers and activators of transcription 3 (Stat3) phosphorylation and reduced PI3-kinase/Akt activity. Restoring phosphatidylinositol 3-kinase (PI3-kinase) but not Stat3 signals reverses the mitogenic defect. CSF-1-induced proliferation and survival are sensitive to glycolytic inhibitors, 2-deoxyglucose and 3-bromopyruvate. Consistent with a critical role for PI3-kinase-regulated glycolysis, DKI cells reconstituted with active PI3-kinase or Akt are hypersensitive to these inhibitors. CSF-1 upregulates hexokinase II (HKII) expression through PI3-kinase, and PI3-kinase transcriptionally activates the HKII promoter. Moreover, HKII overexpression partially restores mitogenicity. In contrast, Bcl-x L expression does not enhance long-term proliferation, although short-term cell death is suppressed in a glycolysis-independent manner. This study identifies robust PI3-kinase activation as essential for optimal CSF-1-mediated mitogenesis in myeloid cells, in part through regulation of HKII and support of glycolysis.

show abstract

STAT-3 Activation Is Required for Normal G-CSF-Dependent Proliferation and Granulocytic Differentiation

Cited by 182 publications

References 47 publications

Differential lymphotoxin-? and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury

Differential lymphotoxin-? and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury

Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction

Colony-stimulating factor-1 requires PI3-kinase-mediated metabolism for proliferation and survival in myeloid cells

Contact Info

Product

Resources

About