用巨噬细胞集落刺激因子刺激人单核细胞可诱导一种由Grb2介导的粘着斑激酶pp125FAK与发动蛋白的结合。

Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin.

作者信息

Kharbanda S, Saleem A, Yuan Z, Emoto Y, Prasad K V, Kufe D

机构信息

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6132-6. doi: 10.1073/pnas.92.13.6132.

DOI:10.1073/pnas.92.13.6132

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC41656/

Abstract

Macrophage colony-stimulating factor (M-CSF) is required for the growth and differentiation of mononuclear phagocytes. In the present studies using human monocytes, we show that M-CSF induces interaction of the Grb2 adaptor protein with the focal adhesion kinase pp125FAK. The results demonstrate that tyrosine-phosphorylated pp125FAK directly interacts with the SH2 domain of Grb2. The findings indicate that a pYENV site at Tyr-925 in pp125FAK is responsible for this interaction. We also demonstrate that the Grb2-FAK complex associates with the GTPase dynamin. Dynamin interacts with the SH3 domains of Grb2 and exhibits M-CSF-dependent tyrosine phosphorylation in association with pp125FAK. These findings suggest that M-CSF-induced signaling involves independent Grb2-mediated pathways, one leading to Ras activation and another involving pp125FAK and a GTPase implicated in receptor internalization.

摘要

巨噬细胞集落刺激因子（M-CSF）是单核吞噬细胞生长和分化所必需的。在目前使用人单核细胞的研究中，我们发现M-CSF可诱导衔接蛋白Grb2与粘着斑激酶pp125FAK相互作用。结果表明，酪氨酸磷酸化的pp125FAK直接与Grb2的SH2结构域相互作用。研究结果表明，pp125FAK中酪氨酸925处的pYENV位点负责这种相互作用。我们还证明，Grb2-FAK复合物与GTP酶发动蛋白相关联。发动蛋白与Grb2的SH3结构域相互作用，并与pp125FAK一起表现出M-CSF依赖性酪氨酸磷酸化。这些发现表明，M-CSF诱导的信号传导涉及独立的Grb2介导的途径，一条导致Ras激活，另一条涉及pp125FAK和一种与受体内化有关的GTP酶。

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2

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Science. 1993 May 28;260(5112):1338-43. doi: 10.1126/science.8493579.

3

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