CANDIDATE LIGAND FOR THE C-KIT TRANSMEMBRANE KINASE RECEPTOR - KL, A FIBROBLAST DERIVED GROWTH-FACTOR STIMULATES MAST-CELLS AND ERYTHROID PROGENITORS
CANDIDATE LIGAND FOR THE C-KIT TRANSMEMBRANE KINASE RECEPTOR - KL, A FIBROBLAST DERIVED GROWTH-FACTOR STIMULATES MAST-CELLS AND ERYTHROID PROGENITORS
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DOI：
10.1002/j.1460-2075.1990.tb07528.x
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发表时间：
1990-10-01
期刊：
影响因子：
11.4
通讯作者：
BESMER, P
中科院分区：
文献类型：
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作者：
NOCKA, K;BUCK, J;BESMER, P
c-kit原癌基因编码一种未知配体的跨膜酪氨酸激酶受体，并与小鼠白斑位点等位(W)。W突变影响黑素形成、配子发生和造血在发育和成年生活。造血W突变的细胞靶点包括红细胞和肥大细胞系以及干细胞中的不同细胞群。在缺乏白细胞介素-3 （IL-3）的情况下，来自正常小鼠而不是W突变小鼠的肥大细胞可以通过与3T3成纤维细胞共培养来维持。基于3T3成纤维细胞共培养系统中W肥大细胞的增殖反应缺陷，提出成纤维细胞产生c-kit配体。我们使用肥大细胞增殖试验从Balb/3T3成纤维细胞条件培养基中纯化30kd蛋白，指定为KL，以达到明显的均匀性。虽然正常和突变的肥大细胞对IL-3的反应相似，但KL刺激正常骨髓来源的肥大细胞的增殖，而不是W小鼠的肥大细胞。从正常小鼠腹腔提取的结缔组织型肥大细胞在其表面表达高水平的c-kit蛋白，并在KL的作用下增殖，同时研究了KL对红系祖细胞的影响。与促红细胞生成素联合使用，KL可刺激胎肝和脾细胞的早期红细胞祖细胞（BFU-E），但不能刺激成年小鼠的骨髓细胞和W/W小鼠的胎肝细胞。综上所述，在肥大细胞生物学和红细胞生成方面，KL的生物学特性与c-kit配体的生物学特性一致，因此，KL可能是c-kit受体的配体。
The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor for an unidentified ligand and is allelic with the murine white-spotting locus (W). W mutations affect melanogenesis, gametogenesis and hematopoiesis during development and in adult life. Cellular targets of W mutations in hematopoiesis include distinct cell populations in the erythroid and mast cell lineages as well as stem cells. In the absence of interleukin-3 (IL-3) mast cells derived from normal mice but not from W mutant mice can be maintained by co-culture with 3T3 fibroblasts. Based on the defective proliferative response of W mast cells in the 3T3 fibroblast co-culture system it had been proposed that fibroblasts produce the c-kit ligand. We have used a mast cell proliferation assay to purify a 30 kd protein, designated KL, from conditioned medium of Balb/3T3 fibroblasts to apparent homogeneity. KL stimulates the proliferation of normal bone marrow derived mast cells but not mast cells from W mice, although both normal and mutant mast cells respond similarly to IL-3. Connective tissue-type mast cells derived from the peritoneal cavity of normal mice were found to express a high level of c-kit protein on their surface and to proliferate in response to KL. The effect of KL on erythroid progenitor cells was investigated as well. In combination with erythropoietin, KL was found to stimulate early erythroid progenitors (BFU-E) from fetal liver and spleen cells but not from bone marrow cells of adult mice and from fetal liver cells of W/W mice. Taken together, the biological properties of KL are in agreement with those expected of the ligand of c-kit with regard to mast cell biology and aspects of erythropoiesis, and therefore, KL may be the ligand of the c-kit receptor.