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The role of Src family kinases in mediating M-CSF receptor signaling and monocytic cell survival

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DOI: 10.4236/abb.2012.35077    3,273 Downloads   5,867 Views   Citations

ABSTRACT

Previously, we reported that M-CSF induced monocyte survival through the activation of Akt, p38MAPK and Erk1/2 kinases. Here, we found that Src family kinases were upstream of these kinases and played a central role in regulating M-CSF-induced monocyte survival. We observed that M-CSF promoted c-Src activation in monocytes and MDMs in a time-dependent manner. Src inhibitors reduced M-CSF-mediated phosphorylation of the M-CSF receptor (M-CSFR), Akt, Erk1/2, and p38 MAPK. We also observed that Src directly phosphorylated the M-CSFR. Notably, the inhibitors blocked phosphorylation of specific tyrosine residues within the M-CSFR. We further demonstrated that the Src inhibitor, PP2, attenuated M-CSF-induced NF-κB activation and M-CSF-induced monocyte survival. These findings indicated that Src family kinases mediate monocyte survival through the regulation of receptor phosphorylation and modulation of downstream signaling events. Thus, we predict that targeting Src family kinases may have therapeutic implication in inflammatory diseases.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Wang, Y. , Piper, M. and Marsh, C. (2012) The role of Src family kinases in mediating M-CSF receptor signaling and monocytic cell survival. Advances in Bioscience and Biotechnology, 3, 592-602. doi: 10.4236/abb.2012.35077.

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