Colony-stimulating factor-1–induced oscillations in phosphatidylinositol-3 kinase/AKT are required for caspase activation in monocytes undergoing differentiation into macrophages

Jacquel, Arnaud; Benikhlef, Naïma; Paggetti, Jérôme; Lalaoui, Najoua; Guéry, Leslie; Dufour, Erick K.; Ciudad, Marion; Racoeur, Cindy; Micheau, Olivier; Delva, Laurent; Droin, Nathalie; Solary, Éric

doi:10.1182/blood-2009-03-208843

Cited by 53 publications

(71 citation statements)

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“…Erk1/2 was activated with coordinated kinetics, but was not essential for nucleophosmin cleavage, and its role remains to be defined. In contrast, the SFKs, Hck, and, to a lesser extent, Lyn, but not Fyn or Src, mediated nucleophosmin cleavage downstream from CSF-1R (Jacquel et al 2009). …”

Section: Csf-1 Receptor Signaling In Myeloid Cellsmentioning

confidence: 91%

“…4C), CSF-1 triggers a cyclic activation of the PI3K and Erk1/2 pathways that is correlated with successive rounds of CSF-1R Tyr-723 phosphorylation and dephosphorylation. Successive waves of Akt activation, increasing in amplitude and duration, are required for caspase activation, which, via cleavage of nucleophosmin, enhances macrophage differentiation (Jacquel et al 2009) toward a trophic, M2-like phenotype (Guery et al 2011). Erk1/2 was activated with coordinated kinetics, but was not essential for nucleophosmin cleavage, and its role remains to be defined.…”

Section: Csf-1 Receptor Signaling In Myeloid Cellsmentioning

confidence: 99%

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CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

607

521

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The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.

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Section: Csf-1 Receptor Signaling In Myeloid Cellsmentioning

confidence: 91%

Section: Csf-1 Receptor Signaling In Myeloid Cellsmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

607

521

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“…Human peripheral blood monocytes were obtained from healthy donors with informed consent according to recommendations of an independent scientific review board, in accordance with the Declaration of Helsinki. Cells were enriched by the use of a monocyte isolation kit with auto-MACS Separator according to themanufacturer's instructions (Miltenyi Biotec) and cultured as previously described (16).…”

Section: Cell Linesmentioning

confidence: 99%

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

Colin

Limagne²,

Jeanningros³

et al. 2011

Cancer Prevention Research

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trans-Resveratrol has been proposed to prevent tumor growth and to sensitize cancer cells to anticancer agents. Polyphenol entry into the cells has remained poorly understood. Here, we show that [ 3 H]-resveratrol enters colon cancer cells (SW480, SW620, HT29) and leukemia U937 cells through a monensin (5-20 mmol/L) -sensitive process that suggests clathrin-independent endocytosis. Uptake of the molecule can be prevented by methyl-b-cyclodextrin (2-12 mg/mL), nystatin (12 ng/mL), and filipin (1 mg/mL), which all disrupt plasma membrane lipid rafts. Accordingly, radiolabeled resveratrol accumulates in sphingomyelin-and cholesterol-enriched cell fractions. Interestingly, extracellular signalregulated kinases (ERK), c-Jun NH 2 -terminal kinases (JNK), and Akt also accumulate in lipid rafts on resveratrol exposure (IC 50 at 48 h % 30 mmol/L in SW480 and U937 cells). In these rafts also, resveratrol promotes the recruitment, by the integrin a V b 3 (revealed by coimmunoprecipitation with an anti-integrin a V b 3 antibody), of signaling molecules that include the FAK (focal adhesion kinase), Fyn, Grb2, Ras, and SOS proteins. Resveratrol-induced activation of downstream signaling pathways and caspase-dependent apoptosis is prevented by endocytosis inhibitors, lipid raft-disrupting molecules, and the integrin antagonist peptide arginine-glycine-aspartate (500 nmol/L). Altogether, these data show the role played by lipid rafts in resveratrol endocytosis and activation of downstream pathways leading to cell death.

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“…4 Previous studies have established that physiological monocyte differentiation triggered by CSF1R (colony stimulating factor 1 receptor) engagement is critically dependent on the formation of a multimolecular complex consisting of FADD (Fas [TNFRSF6]-associated via death domain), CFLAR/FLIP (CASP8 and FADD-apoptosis regulator), CASP8/caspase-8, RIPK1 (receptor [TNFRSF]-interacting serine-threonine kinase 1) and other protein partners; CASP8 acts as the initiatory caspase in this process. 5,6 More recently, we have established that autophagy also plays a crucial role during CSF1-induced differentiation of monocytes. 7,8 Autophagy (macroautophagy) is an evolutionarily conserved catabolic pathway that delivers cytoplasmic substrates, such as damaged organelles and cytoplasmic proteins, to lysosomes for degradation.…”

Section: Introductionmentioning

confidence: 99%

The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML

Obba

Hizir²,

Boyer

et al. 2015

Autophagy

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These authors contributed equally to this work.Keywords: autophagy, CMML, CSF1, differentiation, primary monocyte, PRKAA1/AMPKa1, P2RY6Abbreviations: ACTB actin, b; CAMKK2, calcium/calmodulin-dependent protein kinase kinase 2, b; CASP8, caspase 8; apoptosisrelated cysteine peptidase; CFLAR CASP8 and FADD-like apoptosis regulator; CMML chronic myelomonocytic leukemia; CSF1 colony stimulating factor 1 (macrophage); CSF1R colony stimulating factor 1 receptor; DEFA1 defensin a 1; DEFA3 defensin a 3 neutrophil-specific; DRS; dorsomorphin; EMR1 EGF-like module-containing mucin-like hormone receptor-like 1; FADD Fas (TNFRSF6)-associated via death domain; ITGAM integrin a M; MAP1LC3B/LC3B microtubule-associated protein 1 light chain 3 b; P2RY6 pyrimidinergic receptor P2Y; G-protein coupled 6; PLCB3 phospholipase C; b 3 (phosphatidylinositol-specific); PLC phospholipase; PLCG2 phospholipase C gamma 2 (phosphatidylinositol-specific); PRKAA protein kinase AMP-activated; PRKAA1 protein kinase AMP-activated a 1 catalytic subunit; PRKAA2 protein kinase AMP-activated a 2 catalytic subunit; PRKAG1 protein kinase AMP-activated gamma 1 noncatalytic subunit; RIPK1 receptor (TNFRSF)-interacting serine-threonine kinase 1; STK11 serine/ threonine kinase 11; TFRC transferrin receptor; UDP uridine diphosphate; ULK1 unc-51 like autophagy activating kinase 1; WT wild-type.Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF-1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signaling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML.

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Colony-stimulating factor-1–induced oscillations in phosphatidylinositol-3 kinase/AKT are required for caspase activation in monocytes undergoing differentiation into macrophages

Cited by 53 publications

References 50 publications

CSF-1 Receptor Signaling in Myeloid Cells

CSF-1 Receptor Signaling in Myeloid Cells

Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells

The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML

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