Association between phosphatidylinositol-3 kinase, Cbl and other tyrosine phosphorylated proteins in colony-stimulating factor-1-stimulated macrophages.
Association between phosphatidylinositol-3 kinase, Cbl and other tyrosine phosphorylated proteins in colony-stimulating factor-1-stimulated macrophages.
复制标题
集落刺激因子 1 刺激的巨噬细胞中磷脂酰肌醇 3 激酶、Cbl 和其他酪氨酸磷酸化蛋白之间的关联。
DOI：
--
复制
发表时间：
1996
影响因子：
4.1
通讯作者：
John A. Hamilton
中科院分区：
文献类型：
--
作者：
V. Kanagasundaram;Anthony Jaworowski;John A. Hamilton
集落刺激因子-1（CSF-1）对巨噬细胞系BAC 1.2F5和小鼠骨髓源性巨噬细胞的刺激导致磷脂酰肌醇-3激酶（PI-3激酶）p85 α的酪氨酸磷酸化及其与几种酪氨酸磷酸化蛋白（包括CSF-1受体（p165）、p120、p95和p55-p60）的稳定结合。p120在抗p85 α免疫沉淀物中与原癌基因c-cb 1的产物共迁移，并以快速和瞬时的方式与p85 α结合。相互实验证实了p85 α在抗Cb 1免疫沉淀物中对巨噬细胞的CSF-1刺激的存在。PI-3激酶免疫沉淀来自表达突变CSF-1受体（Y 721 F）的髓样FDC-P1细胞系，其不与PI-3激酶结合，仍然含有Cbl。酪氨酸磷酸化蛋白p95的身份仍然未知。p85 α和酪氨酸磷酸化蛋白之间的相互作用在阴离子交换色谱中存活下来，这表明可能存在稳定的复合物;此外，在CSF-1处理的BAC 1.2F5细胞提取物中，通过色谱分离的PI-3激酶的两个池中只有一个存在于这个推定的复合物中。这种关联似乎与增殖无关，因为在用CSF-1刺激的增殖不良的驻留腹腔巨噬细胞中也观察到p85 α和酪氨酸磷酸化蛋白之间的类似相互作用。CSF-1调节的巨噬细胞功能，这些研究结果的可能意义进行了讨论。
Colony stimulating factor-1 (CSF-1) stimulation of the macrophage cell line BAC1.2F5 and murine bone marrow-derived macrophages resulted in tyrosine phosphorylation of phosphatidylinositol-3 kinase (PI-3 kinase) p85 alpha and its stable association with several tyrosine phosphorylated proteins, including CSF-1 receptor (p165), p120, p95 and p55-p60. p120 co-migrated with the product of the protooncogene c-cb1 in anti-p85 alpha immunoprecipitates, and associated with p85 alpha in a rapid and transient manner. Reciprocal experiments confirmed the presence of p85 alpha in anti-Cb1 immunoprecipitates on CSF-1 stimulation of macrophages. PI-3 kinase immunoprecipitates from the myeloid FDC-P1 cell line expressing mutant CSF-1 receptor (Y721F), which does not associate with PI-3 kinase, still contained Cbl. The identity of the tyrosine phosphorylated protein p95 remains unknown. The interaction between p85 alpha and the tyrosine phosphorylated proteins survived anion-exchange chromatography, suggesting perhaps the presence of a stable complex; furthermore, in CSF-1-treated BAC1.2F5 cell extracts, only one of the two pools of PI-3 kinase separated by chromatography was present in this putative complex. The association did not appear to correlate with proliferation, since a similar interaction between p85 alpha and tyrosine phosphorylated proteins was also observed in poorly proliferating resident peritoneal macrophages stimulated with CSF-1. The possible significance of these findings for CSF-1-regulated macrophage functions is discussed.