MONOCYTE DIFFERENTIATION: ROLE OF TYROSINE PHOSPHORYLATION VIA CSF-1 RECEPTOR

将c-FMS基因导入小鼠造血细胞系32D， 它编码CSF-1受体，一种酪氨酸激酶(TK)。在 缺乏CSF-1，转基因细胞显示中等水平的花生四烯酸 酸(A.A)释放并产生大量前列腺素E_2 (PGE2)与原始细胞系比较。暴露于 转染细胞至CSF-1，同时诱导显著增加 然而，花生四烯酸的释放导致PGE2的抑制 制作。向细胞中添加酪氨酸激酶抑制剂ST638 不含CSF-1的c-FMS基因可抑制前列腺素E_2的产生 在10到60分钟内。它添加到存在的相同细胞中 脑脊液-1的作用相反，但需要更长的治疗时间(24 小时)。在任何一种细胞类型中，A.A.的释放都不受此影响 探员。这些数据表明，脑脊液-！受体可能参与调节 环氧合酶活性。脑脊液-1受体对前列腺素E_2的不同作用 在有或没有CSF-1的情况下产生和相反的效应 对PGE2的酪氨酸激酶抑制剂的研究表明， 单独或受体-配体复合体转导一种活性的但不同的， 通过酪氨酸磷酸化来传递信号。

The mouse hematopoietic cell line, 32D, was transfected with c-fms, which encodes for the CSF-1 receptor, a tyrosine kinase (TK). In the absence of CSF-1, transfected cells show moderate levels of arachidonic acid (A.A) release and produce a substantial amount of prostaglandin E2 (PGE2 in comparison with the original cell line. Exposure of transfected cells to CSF-1, while inducing a substantial increase in arachidonate release, nevertheless resulted in inhibition of PGE2 production. Addition of ST638, a tyrosine kinase inhibitor, to cells transfected with c-fms in the absence of CSF-1 inhibited PGE2 production within 10 to 60 minutes. Its addition to the same cells in the presence of CSF-1 induced an opposite effect, but required longer treatment (24 hours). In either cell type, A.A. release was not affected by this agent. These data indicate that CSF-! receptor may regulate cyclooxygenase activity. The different effect of CSF-1 receptor on PGE2 production in the presence or absence of CSF-1 and the opposite effect of a tyrosine kinase inhibitor on PGE2 suggest that both the receptor alone or the receptor-ligand complex transduce an active, but different, signal through tyrosine phosphorylation.