Induced Expression and Association of the Mona/Gads Adapter and Gab3 Scaffolding Protein during Monocyte/Macrophage Differentiation

Bourgin, Caroline; Bourette, Roland P.; Arnaud, Sylvie; Liu, Yan; Rohrschneider, Larry R.; Mouchiroud, Guy

doi:10.1128/mcb.22.11.3744-3756.2002

Cited by 37 publications

(40 citation statements)

References 60 publications

(119 reference statements)

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“…28 While HPK1-N cells already react to M-CSF stimulation (Figure 2d) and express the M-CSFR (Figure 3c), M-CSFR triggered pathways may function inefficiently. 20,29,30 Caspase cleavage of HPK1 was shown to modulate its function in lymphocytes. 8,14 In contrast, little is known about the role of HPK1 in myeloid cells.…”

Section: Discussionmentioning

confidence: 99%

Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

et al. 2006

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We studied monocytic differentiation of primary mouse progenitor cells to understand molecular mechanisms of differentiation. We found a tightly controlled non-apoptotic activation of caspase-3 that correlated with differentiation. Although caspase activity was already detected during monocytic differentiation, a caspase-3 target has not been identified yet. We show that hematopoietic progenitor kinase 1 (HPK1) is processed towards its N-and C-terminal fragments during monocytic differentiation. While HPK1 is an immunoreceptor-proximal kinase in T and B cells, its role in myeloid cells is elusive. Here, we show that the N-terminal cleavage product, HPK1-N, comprising the kinase domain, confers progenitor cell survival independent of the growth factor IL-3. Furthermore, HPK1-N causes differentiation of progenitor cells towards the monocytic lineage. In contrast to full-length kinase, HPK1-N is constitutively active causing sustained JNK activation, Bad phosphorylation and survival. Blocking of caspase activity during differentiation of primary mouse progenitor cells leads to reduced HPK1-N levels, suppressed JNK activity and attenuated monocytic differentiation. Our work explains growth factor-independent survival during monocytic differentiation by caspase-mediated processing of HPK1 towards HPK1-N. Cell Death and Differentiation (2007) 14, 568-575. doi:10.1038/sj.cdd.4402042; published online 6 October 2006Within the hematopoietic system lineage commitment, differentiation and proliferation are precisely balanced throughout life, resulting in adjusted levels of myeloid and lymphoid cells. A complicated network of cytokines essentially contributes to hematopoietic homeostasis. Myeloid progenitor cells and myeloid-like cell lines respond to the cytokine interleukine-3 (IL-3) with proliferation and survival. 1 While removal of IL-3 results in cell death via apoptosis, suppression of apoptosis allows differentiation of the mouse hematopoietic progenitor cell line FDC-P1 in the absence of IL-3. 2 Monocytic differentiation of primary bone marrow and fetal liver progenitors or myeloid cell lines can be induced by IL-3 withdrawal and stimulation with monocyte-colony stimulating factor (M-CSF). 3 Monocytic differentiation is accompanied by caspase activation; 4,5 however, the molecular targets of caspase activity during monocytic differentiation have not been identified.Hematopoietic progenitor kinase 1 (HPK1) is comprised of a catalytic domain with extensive homology to the Sterile 20 kinase of the yeast Saccharomyces cerevisiae and a Cterminally located regulatory domain, called citron homology domain. 6 Ectopic expression renders full-length HPK1 active in epithelial cells resulting in selective activation of the JNK and the NFkB pathways. 7,8 Upon caspase-3 cleavage the N-terminal kinase domain of HPK1 (HPK1-N) is separated from the C-terminus (HPK1-C) resulting in suppression of NFkB. 8 In non-stimulated lymphocytes, HPK1 kinase activity is hardly detectable, but antigen receptor crosslinking leads to profound HPK1...

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Section: Discussionmentioning

confidence: 99%

Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

et al. 2006

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“…However, only the late wave, which is independent of Grb2/Sos assembly or PI 3-kinase activity, is required for macrophage differentiation (Gobert Gosse et al 2005). Mona, an adaptor protein that increases late Erk1/2 phosphorylation (Bourgin et al 2002) and Gab3 are coinduced during monocytic differentiation in a CSF-1R Tyr-807-dependent manner (Fig. 4A).…”

Section: Er Stanley and V Chitumentioning

confidence: 99%

“…Mona interacts with Gab3 and with the CSF-1R pTyr-697 site. This site is also important for Gab3 tyrosine phosphorylation, induction of Mona expression, and macrophage differentiation (Bourgin et al 2002). Gab proteins interact with Shp2 and mediate Erk1/2 activation downstream from growth factor receptors (Nishida et al 1999;Meng et al 2005;Lee et al 2011).…”

Section: Er Stanley and V Chitumentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

613

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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“…8,26 Thus, addition of the MEK inhibitor U0126 could be delayed by 24 h after the beginning of M-CSF stimulation while being still able to block M-CSF differentiation signal. 8 This prompted us to perform delayed PP2 addition experiments on M-CSF stimulation of FD-Fms cells.…”

Section: Macrophage Differentiation Requires Late and Sustained Sfk Amentioning

confidence: 99%

“…Flow cytometry determination of Mac-2 expression on FD-Fms cells was performed by indirect immunofluorescence as previously described. 26 Mac2 antibody and FITC-conjugated F(ab 0 ) 2 fragment goat anti-rat immunoglobulin G were from Cedarlane and Caltag Laboratories (Burlingame, CA, USA), respectively. Cultivated BMMC were labeled by direct immunofluorescence according to instructions from antibody manufacturers.…”

Section: Morphological and Flow Cytometric Analysesmentioning

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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Induced Expression and Association of the Mona/Gads Adapter and Gab3 Scaffolding Protein during Monocyte/Macrophage Differentiation

Cited by 37 publications

References 60 publications

Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

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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