A Juxtamembrane Tyrosine in the Colony Stimulating Factor-1 Receptor Regulates Ligand-induced Src Association, Receptor Kinase Function, and Down-regulation

Rohde, Cynthia M.; Schrum, Jason; Lee, Angel W.-M.

doi:10.1074/jbc.m314170200

Cited by 56 publications

(56 citation statements)

References 79 publications

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“…6 The CSF-1R also recruits Src kinases via an autophosphorylation site in the juxtamembrane domain. 7,8 The kinase insert (KI) region in the CSF-1R has binding sites for Grb2/Mona, Stat1 and PI3-kinase. 9 CSF-1-provoked Erk and PI3-kinase activities, however, are not exclusively dependent on these sites: when expressed in the 32D myeloid progenitor cell line, the DKI mutant lacking the KI can still activate Erk and PI3-kinase.…”

Section: Introductionmentioning

confidence: 99%

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

Lee

States

2006

Cell Death Differ

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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.

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Section: Introductionmentioning

confidence: 99%

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

Lee

States

2006

Cell Death Differ

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“…Inhibition is relieved by phosphorylation of Tyr-561 (Tyr-559 in mouse). This tyrosine, the first residue to be phosphorylated in response to ligand binding, acts as a switch that is off in the absence of ligand and turned on by phosphorylation in response to ligand (Rohde et al 2004;Yu et al 2008;Xiong et al 2011;Yu et al 2012). Although the structure of the activated CSF-1R kinase domain has not been reported, the changes that take place on activation can be visualized by superimposing the AL of activated cKIT onto inactive CSF-1R structure (Schubert et al 2007;Chitu and Stanley 2014).…”

Section: Csf-1r Kinase Structure and Activationmentioning

confidence: 99%

“…JMD Tyr-559 is the first tyrosine phosphorylated in response to ligand (Yu et al 2008;Xiong et al 2011). Tyr-559 keeps CSF-1R kinase "off " in the absence of ligand and its phosphorylation relieves this autoinhibition, so that Tyr-559 controls CSF-1R responsiveness to ligand (Rohde et al 2004;Takeshita et al 2007;Yu et al 2012). JMD Tyr-544, phosphorylated in the oncogenic receptor (Joos et al 1996), is required for full kinase activation (Yu et al 2008).…”

Section: Role Of Individual Csf-1r Intracellular Domain Phosphotyrosimentioning

confidence: 99%

“…Tyr-559 is both necessary and sufficient for the recruitment of SFK that, in turn, associate with and activate c-Cbl. Cbl activation leads to CSF-1R multiubiquitination, conformational changes, increased phosphorylation, and internalization of receptor-ligand complexes (Baccarini et al 1991;Rohde et al 2004;Xiong et al 2011). Tyr-721 is necessary and sufficient on the YEF.Y544,559,807AB background, for mediating macrophage chemotaxis to CSF-1 through the PI3K pathway (Sampaio et al 2011).…”

Section: Role Of Individual Csf-1r Intracellular Domain Phosphotyrosimentioning

confidence: 99%

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CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

635

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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“…19 In the FD-Fms model, activation of MAPK 8 or phospholipase C-g2 (PLC-g2) 20 is required for macrophage differentiation. Studies with M1 and 32D murine myeloid cell lines demonstrated Src-family kinases (SFK) binding to activated M-CSFR 21 and partial impairment of M-CSF-induced differentiation by the src kinase inhibitor PP2. 22 In addition to activation of specific signaling pathways, another important aspect of M-CSF signaling specificity is the strength and duration of signaling.…”

Section: Introductionmentioning

confidence: 99%

Src-family kinases play an essential role in differentiation signaling downstream of macrophage colony-stimulating factor receptors mediating persistent phosphorylation of phospholipase C-γ2 and MAP kinases ERK1 and ERK2

et al. 2007

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Macrophage colony-stimulating factor (M-CSF) has been found to be involved in multiple developmental processes, especially production of cells belonging to the mononuclear phagocyte system. The decision of myeloid progenitor cells to commit to differentiation depends on activation levels of the mitogenactivated protein kinases (MAPK), ERK1 and ERK2. Using the murine myeloid progenitor cell line FD-Fms, we show here that persistent activity of Src-family kinases (SFK) is necessary for FD-Fms cell differentiation to macrophages in response to M-CSF. Chemical inhibition of SFK blocked FD-Fms cell differentiation while it caused strong inhibition of the late phosphorylation of phospholipase C (PLC)-c2 and MAPK. The PLC inhibitor U73122, previously shown to block M-CSF-induced differentiation, strongly decreased long-term MAPK phosphorylation. Interestingly, inhibiting SFK with SU6656 or the MAPK kinases MEK with U0126 significantly impaired development of mononuclear phagocytes in cultures of mouse bone marrow cells stimulated with M-CSF. Collectively, results support a model in which SFK are required for sustained PLC activity and MAPK activation above threshold required for commitment of myeloid progenitors to macrophage differentiation.

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A Juxtamembrane Tyrosine in the Colony Stimulating Factor-1 Receptor Regulates Ligand-induced Src Association, Receptor Kinase Function, and Down-regulation

Cited by 56 publications

References 79 publications

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

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

CSF-1 Receptor Signaling in Myeloid Cells

Src-family kinases play an essential role in differentiation signaling downstream of macrophage colony-stimulating factor receptors mediating persistent phosphorylation of phospholipase C-γ2 and MAP kinases ERK1 and ERK2

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