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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The murine stk gene product, a transmembrane protein tyrosine kinase, is a receptor for macrophage-stimulating protein.
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The murine stk gene product, a transmembrane protein tyrosine kinase, is a receptor for macrophage-stimulating protein.

机译：鼠stk基因产物是跨膜蛋白酪氨酸激酶，是巨噬细胞刺激蛋白的受体。

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摘要

Macrophage-stimulating protein (MSP) was originally identified as an inducer of murine resident peritoneal macrophage responsiveness to chemoattractants. We recently showed that the product of RON, a protein tyrosine kinase cloned from a human keratinocyte library, is the receptor for MSP. Similarity of murine stk to RON led us to determine if the stk gene product is the murine receptor for MSP. Radiolabeled MSP could bind to NIH 3T3 cells transfected with murine stk cDNA (3T3/stk). Binding was saturable and was inhibited by unlabeled MSP but not by structurally related proteins, including hepatocyte growth factor and plasminogen. Specific binding to STK was demonstrated by cross-linking of 125I-labeled MSP to membrane proteins of 3T3/stk cells, which resulted in a protein complex with a molecular mass of 220 kDa. This radiolabeled complex comprised 125I-MSP and STK, since it could be immunoprecipitated by antibodies to the STK beta chain. Binding of MSP to stk cDNA-transfected cells induced tyrosine phosphorylation of the 150-kDa STK beta chain within 1 min and caused increased motile activity. These results establish the murine stk gene product as a specific transmembrane protein tyrosine kinase receptor for MSP. Inasmuch as the stk cDNA was cloned from a hematopoietic stem cell, our data suggest that in addition to macrophages and keratinocytes, a cell in the hematopoietic lineage may also be a target for MSP.
机译：巨噬细胞刺激蛋白（MSP）最初被确定为鼠驻地腹膜巨噬细胞对趋化因子反应性的诱导剂。我们最近表明，RON（从人角质形成细胞文库中克隆的蛋白质酪氨酸激酶）的产物是MSP的受体。鼠stk与RON的相似性使我们确定stk基因产物是否为MSP的鼠受体。放射性标记的MSP可以与鼠stk cDNA（3T3 / stk）转染的NIH 3T3细胞结合。结合是可饱和的，并且不受未标记的MSP抑制，但不受结构相关蛋白（包括肝细胞生长因子和纤溶酶原）的抑制。通过将125 I标记的MSP交联到3T3 / stk细胞的膜蛋白上，证明了与STK的特异性结合，这导致了分子量为220 kDa的蛋白复合物。该放射性标记的复合物包含125I-MSP和STK，因为它可以被STKβ链的抗体免疫沉淀。 MSP与stk cDNA转染的细胞的结合在1分钟内诱导了150 kDa STKβ链的酪氨酸磷酸化，并导致运动活性增加。这些结果确立了鼠stk基因产物作为MSP的特异性跨膜蛋白酪氨酸激酶受体。由于从造血干细胞克隆了stk cDNA，我们的数据表明，除巨噬细胞和角质形成细胞外，造血谱系中的细胞也可能是MSP的靶标。

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