CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2

Husson, Hervé; Mograbi, Baharia; Schmid-Antomarchi, Heidy; Fischer, Siegmund; Rossi, Bernard

doi:10.1038/sj.onc.1201074

Cited by 34 publications

(21 citation statements)

References 28 publications

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“…Indeed, following Fms activation, Grb2 was reported to form a complex with Sos, the focal adhesion kinase, Cbl, and dynamine (Kharbanda et al, 1995;Husson et al, 1997). Therefore, it is possible that some of these additional proteins are directly engaged in the degradation of the ®bronectin network.…”

Section: Discussionmentioning

confidence: 99%

Identification of a second Grb2 binding site in the v-Fms tyrosine kinase

et al. 1997

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Tyrosine autophosphorylation of the v-Fms oncogene product results in the formation of high-a nity binding sites for cellular proteins containing Src homology 2 (SH2) domains. These proteins transduce various mitogenic and morphogenic signals. As reported previously, Y 696 KNI in the kinase insert domain of v-Fms binds to the growth factor receptor bound protein 2 (Grb2), a stimulator of the Ras/Raf1 pathway. Here, we mapped Y 921 TNL within the C-terminal domain of Fms as a novel autophosphorylation site. We demonstrate that this site constitutes a second Grb2 binding site: a recombinant fusion protein (residues 904 ± 944) containing phosphorylated Y921 bound Grb2 from FDCP1Mac11 cell extracts signi®cantly more e ciently than a corresponding protein (residues 617 ± 759) containing Y696. A yeast two-hybrid system which allowed the formation of a functional Fms tyrosine kinase was employed to quantify binding of Grb2. Fms-protein containing either one of the two phosphorylation sites bound Grb2 equally well, binding was increased for proteins carrying both sites. In contrast, the simultaneous substitution of Y696 and Y921 by phenylalanines abolished Grb2 binding. Mouse NIH3T3 cells expressing the Y921F mutant Fms-protein showed a substantially higher content of ®bronectin network than wild-type transformed cells and had largely lost their serum independent growth phenotype.

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Section: Discussionmentioning

confidence: 99%

Identification of a second Grb2 binding site in the v-Fms tyrosine kinase

et al. 1997

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“…Before CSF-1 addition, CSF-1Rs are clustered, or are undergoing a rapid dimer-monomer transition . CSF-1 binding initially leads to rapid dimerization, a first wave of tyrosine phosphorylation of the CSF-1R, and formation of CSF-1R complexes with Grb2/Sos and with SFK, Cbl, the regulatory subunit of PI-3 kinase (PI3K) ( p85), Grb2, and other signaling molecules, many of which become tyrosine phosphorylated (Baccarini et al 1991;Kanagasundaram et al 1996;Wang et al 1996Wang et al , 1999bHusson et al 1997). The tyrosine phosphorylated proteins, representing 0.02% of the total cellular protein, are mainly in the membrane fraction (Yeung et al 1998).…”

Section: Kinetics Of Early Responses In Macrophagesmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

564

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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“…Cbl phosphorylation and its association with other proteins are stimulated in cells after treatment with growth factors such as EGF (17,42), PDGF (1), and colony-stimulating factor (CSF) (10). There is ample evidence that Cbl associates with RTKs (e.g., EGFR, PDGFR, and CSF-1R) and other adapter proteins (e.g., Grb2, Shc, and P85) to activate downstream signaling pathways (21).…”

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confidence: 99%

Interplay between integrins and FLK-1 in shear stress-induced signaling

Wang¹,

Miao²,

Song³

et al. 2002

American Journal of Physiology-Cell Physiology

115

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We studied interactions between integrins and Flk-1 in transducing the mechanical shear stress due to flow. This application of a step shear stress caused Flk-1 ⅐ Casitas B-lineage lymphoma (Cbl) activation (Flk-1 ⅐ Cbl association, tyrosine phosphorylation of the Cbl-bound Flk-1, and tyrosine phosphorylation of Cbl) in bovine aortic endothelial cells (BAECs). The activation of integrins by plating BAECs on vitronectin or fibronectin also induced this Flk-1 ⅐ Cbl activation. The shear-induced Flk-1 ⅐ Cbl activation was blocked by inhibitory antibodies for ␣ v␤3-or ␤1-integrin, suggesting that it is mediated by integrins. Inhibition of Flk-1 by SU1498 also abolished this shear-induced Flk-1 ⅐ Cbl activation. In contrast to the requirement of integrins for Flk-1 ⅐ Cbl activation, the Flk-1 blocker SU1498 had no detectable effect on the shear-induced integrin activation, suggesting that integrins and Flk-1 play sequential roles in the signal transduction hierarchy induced by shear stress. Integrins are essential for the mechanical activation of Flk-1 by shear stress but not for the chemical activation of Flk-1 by VEGF. mechanotransduction; vascular endothelial growth factor; Casitas B-lineage lymphoma MECHANICAL FORCES ARE KNOWN TO PLAY A KEY ROLE in many physiological processes, but how cells perceive mechanical stimuli and convert them into biochemical signaling pathways is not yet well understood. Shear stress, the tangential component of hemodynamic forces acting on the vessel wall, is an important modulator of vascular cell functions in normal and pathophysiological conditions, e.g., endothelial wound healing, atherosclerosis, and reperfusion injury (14,36,37,43). In vitro experiments using endothelial cells (ECs) cultured in flow channels have shown that the structure and function of ECs are modulated by shear stress (6). Recent studies indicate that the mechanochemical transduction in response to shear stress involves different types of receptors and multiple intracellular signaling pathways. Studies from several laboratories, including our own, have demonstrated that shear stress can activate integrins, VEGF receptor-2 (Flk-1), G protein-coupled receptors (GPCR), and ion channels and subsequently regulate mitogen-activated protein kinases and the NF-B pathway through Ras and Rho family GTPases (5,26,33,40). The available evidence indicates that the shear stress-induced signaling from different sensing elements can coordinate downstream signaling through convergent and divergent pathways. However, the possible interaction of these sensing elements in ECs in response to shear stress remains to be investigated.Most intracellular signals are not transduced along a simple linear path involving the interaction of only one molecule with the next. Proteins associate into networks, which are subject to control by many interdependent processes. Many different types of receptors exert mutual influences on each other (9,16,23,30). There is considerable evidence for the synergistic regulation of signals by integrins and...

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CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2

Cited by 34 publications

References 28 publications

Identification of a second Grb2 binding site in the v-Fms tyrosine kinase

Identification of a second Grb2 binding site in the v-Fms tyrosine kinase

CSF-1 Receptor Signaling in Myeloid Cells

Interplay between integrins and FLK-1 in shear stress-induced signaling

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