Distinct role for c-kit receptor tyrosine kinase and SgIGSF adhesion molecule in attachment of mast cells to fibroblasts
Distinct role for c-kit receptor tyrosine kinase and SgIGSF adhesion molecule in attachment of mast cells to fibroblasts
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DOI：
10.1038/labinvest.3700231
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发表时间：
2005-03-01
影响因子：
5
通讯作者：
Kitamura, Y
中科院分区：
文献类型：
--
作者：
Koma, Y;Ito, A;Kitamura, Y
干细胞因子（SCF）与c- kit受体酪氨酸激酶（kit）结合，通过磷脂酰肌醇3-激酶（PI3- K）的激活等多种途径转导肥大细胞发育所必需的信号。当培养的肥大细胞（cmc）与表达膜结合SCF的成纤维细胞共培养时，具有正常KIT的cmc粘附在成纤维细胞上并增殖，而缺乏细胞表面KIT表达的cmc则不会。生精免疫球蛋白超家族（SgIGSF）是另一种参与肥大细胞粘附成纤维细胞的分子。由于IC- 2肥大细胞系既不表达KIT，也不表达SgIGSF，因此我们检测了KIT或SgIGSF异位表达对IC- 2细胞粘附的影响。使用了三种具有正常外结构域的KIT：野生型（KIT- WT）和两种酪氨酸残基上有苯丙氨酸取代的突变型（KIT- Y719F）或821 （KIT- Y821F）。KIT- Y719F不能激活PI3- K，而KIT- Y821F可以。首先，在IC- 2细胞中单独表达KIT或SgIGSF。三种形式的KIT均增加了IC- 2细胞的粘附水平，而SgIGSF则没有。其次，SgIGSF与三种KIT形式中的一种共表达。与KIT- WT或KIT- Y821F共表达SgIGSF比单独表达KIT- WT或KIT- Y821F更显著地提高了粘附水平。这种作用被阻断SCF - KIT相互作用的抗体所消除。相比之下，SgIGSF与KIT- Y719F共表达并没有增加KIT- Y719F单独诱导的粘附水平。在肥大细胞与成纤维细胞的粘附过程中，KIT表现为一种粘附分子，并通过磷酸化PI3- K激活其他粘附分子。
Binding of stem cell factor ( SCF) to c- kit receptor tyrosine kinase ( KIT) transduces signals essential for mast cell development via several pathways including activation of phosphatidylinositol 3- kinase ( PI3- K). When cultured mast cells ( CMCs) are cocultured with fibroblasts expressing membrane- bound SCF, CMCs with normal KIT adhere to fibroblasts and proliferate, whereas CMCs lacking cell surface expression of KIT do neither. Spermatogenic immunoglobulin superfamily ( SgIGSF) was identified as another molecule that participates in mast cell adhesion to fibroblasts. Since the IC- 2 mast cell line expressed neither KIT nor SgIGSF, the effect of ectopic expression of KIT or SgIGSF on the adhesion of IC- 2 cells was examined. Three forms of KIT with the normal ectodomain were used: wild- type ( KIT- WT) and two mutant types with a phenylalanine substitution at the tyrosine residue 719 ( KIT- Y719F) or 821 ( KIT- Y821F). KIT- Y719F does not activate PI3- K, whereas KIT- Y821F does. Firstly, KIT or SgIGSF was expressed singly in IC- 2 cells. All three forms of KIT increased the adhesion level of IC- 2 cells, whereas SgIGSF did not. Secondly, SgIGSF was coexpressed with one of the three forms of KIT. Coexpression of SgIGSF with KIT- WT or KIT- Y821F increased the adhesion level more markedly than was achieved by KIT- WT or KIT- Y821F alone. The effect was abolished by an antibody that blocks SCF - KIT interaction. In contrast, coexpression of SgIGSF with KIT- Y719F did not increase the adhesion level induced by KIT- Y719F alone. In adhesion of mast cells to fibroblasts, KIT appeared to behave as an adhesion molecule and as an activator of other adhesion molecules through phosphorylating PI3- K.