ACTIVATION OF THE HUMAN C-KIT PRODUCT BY LIGAND-INDUCED DIMERIZATION MEDIATES CIRCULAR ACTIN REORGANIZATION AND CHEMOTAXIS
ACTIVATION OF THE HUMAN C-KIT PRODUCT BY LIGAND-INDUCED DIMERIZATION MEDIATES CIRCULAR ACTIN REORGANIZATION AND CHEMOTAXIS
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DOI：
10.1002/j.1460-2075.1991.tb04989.x
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发表时间：
1991-12-01
期刊：
影响因子：
11.4
通讯作者：
HELDIN, CH
中科院分区：
文献类型：
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作者：
BLUMEJENSEN, P;CLAESSONWELSH, L;HELDIN, CH
原癌基因c-kit与鼠白色斑点（W）基因座等位，编码一种跨膜蛋白酪氨酸激酶，其结构与血小板衍生生长因子（PDGF）和集落刺激因子-1（CSF-1）的受体相关。最近，c-kit产物干细胞因子（SCF）的配体以跨膜和可溶形式被鉴定。为了研究SCF激活受体的机制和激活的c-kit产物的生物学特性，我们将野生型人c-kit cDNA转染到猪主动脉内皮细胞中。我们发现，该受体被下调，并传递促有丝分裂信号的刺激与可溶性SCF。我们还表明，SCF诱导的c-kit产品在完整的细胞中的二聚化，和受体的二聚化与其激酶的激活。发现SCF激活c-kit产物诱导的环状肌动蛋白重组与响应PDGF-BB的PDGF β-受体介导的环状肌动蛋白重组难以区分。此外，可溶性SCF是一种有效的趋化剂的细胞表达的c-kit产品，这可能是胚胎发育过程中的重要属性。
The proto-oncogene c-kit is allelic with the murine white spotting (W) locus and encodes a transmembrane protein tyrosine kinase that is structurally related to the receptors for platelet-derived growth factor (PDGF) and colony-stimulating factor-1 (CSF-1). Recently the ligand for the c-kit product, stem cell factor (SCF), was identified in both transmembrane and soluble forms. In order to examine the mechanism for receptor activation by SCF and biological properties of the activated c-kit product, we transfected the wild-type human c-kit cDNA into porcine aortic endothelial cells. We found that the receptor was down-regulated and transmitted a mitogenic signal in response to stimulation with soluble SCF. We also demonstrate that SCF induces dimerization of the c-kit product in intact cells, and that dimerization of the receptor is correlated with activation of its kinase. Activation of the c-kit product by SCF was found to induce circular actin reorganization indistinguishable from that mediated by the PDGF beta-receptor in response to PDGF-BB. Furthermore, soluble SCF was a potent chemotactic agent for cells expressing the c-kit product, a property which might be of importance during embryonic development.