CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Production by RAW264.7 Cells

c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c-fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c-fps/fes did not cause tyrosine phosphorylation or activation of CSF-1 dependent targets, including CSF-1R, Shc, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross-reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c-fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF-1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases.

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Functional specificity of cytoplasmic and transmembrane tyrosine kinases: identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages.

Molecular and Cellular Biology ◽

10.1128/mcb.14.7.4606 ◽

1994 ◽

Vol 14 (7) ◽

pp. 4606-4615 ◽

Cited By ~ 21

Author(s):

L B Areces ◽

P Dello Sbarba ◽

M Jücker ◽

E R Stanley ◽

R A Feldman

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Phosphorylation ◽

Tyrosine Kinases ◽

Protein Tyrosine Kinase ◽

Phosphatidylinositol 3 Kinase ◽

Macrophage Cell ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Stimulating Factor

c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c-fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c-fps/fes did not cause tyrosine phosphorylation or activation of CSF-1 dependent targets, including CSF-1R, Shc, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross-reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c-fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF-1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases.

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Direct analysis of the binding of the abl Src homology 2 domain to the activated epidermal growth factor receptor.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)53920-x ◽

1993 ◽

Vol 268 (3) ◽

pp. 1775-1779 ◽

Cited By ~ 1

Author(s):

G. Zhu ◽

S.J. Decker ◽

B.J. Mayer ◽

A.R. Saltiel

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Direct Analysis ◽

Src Homology 2 ◽

Src Homology ◽

Epidermal Growth ◽

Src Homology 2 Domain

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Evidence for autoinhibitory regulation of the c-src gene product. A possible interaction between the src homology 2 domain and autophosphorylation site.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)54051-5 ◽

1993 ◽

Vol 268 (2) ◽

pp. 1132-1140

Author(s):

Y. Fukami ◽

K. Sato ◽

K. Ikeda ◽

K. Kamisango ◽

K. Koizumi ◽

...

Keyword(s):

Gene Product ◽

Src Homology 2 ◽

Src Gene ◽

Src Homology ◽

Src Homology 2 Domain ◽

Autophosphorylation Site

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Investigating the reason for loss-of-function of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) caused by Y279C mutation through molecular dynamics simulation

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2019.1634641 ◽

2019 ◽

Vol 38 (9) ◽

pp. 2509-2520 ◽

Cited By ~ 2

Author(s):

Wen-Shan Liu ◽

Rui-Rui Wang ◽

Wei-Ya Li ◽

Mei Rong ◽

Chi-Lu Liu ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Dynamics Simulation ◽

Loss Of Function ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain

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IL-6 blocks a discrete early step in lymphopoiesis

Blood ◽

10.1182/blood-2005-02-0456 ◽

2005 ◽

Vol 106 (3) ◽

pp. 879-885 ◽

Cited By ~ 48

Author(s):

Kazuhiko Maeda ◽

Yoshihiro Baba ◽

Yoshinori Nagai ◽

Kozo Miyazaki ◽

Alexander Malykhin ◽

...

Keyword(s):

Target Cells ◽

Hematopoietic Progenitors ◽

Early Step ◽

Hematopoietic Stem ◽

Lymphoid Lineage ◽

Src Homology 2 ◽

Multipotent Progenitors ◽

Src Homology ◽

Src Homology 2 Domain

Abstract Animals lacking Src homology 2 domain-containing inositol 5-phosphatase (SHIP) display a reduction in lymphopoiesis and a corresponding enhancement of myelopoiesis. These effects are mediated at least in part by elevated levels of interleukin 6 (IL-6). Here, we show the lymphopoiesis block in SHIP–/– mice is due to suppression of the lymphoid lineage choice by uncommitted progenitors. The suppression can be reproduced in vitro with recombinant IL-6, and IL-6 acts directly on hematopoietic progenitors. The block is partially overcome in SHIP–/– IL-6–/– double-deficient animals. IL-6 does not suppress but actually enhances proliferation of lymphoid-committed progenitors, indicating the IL-6 target cells are hematopoietic stem cells or multipotent progenitors. The findings suggest a mechanism for the lymphopenia that accompanies proinflammatory diseases.

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