The DING protein: an autocrine growth-stimulatory protein related to the human synovial stimulatory protein

The DING protein: an autocrine growth-stimulatory protein related to the human synovial stimulatory protein
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DOI:
10.1016/s0925-4439(01)00104-1
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发表时间:
2002-04-24
影响因子:
6.2
通讯作者:
Scott, K
Scott, K
中科院分区:
生物学2区
文献类型:
--
作者:
Adams, L;Davey, S;Scott, K

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滑膜刺激蛋白(SSP)先前已从类风湿性关节炎的滑膜液和类风湿性关节炎的滑膜成纤维细胞培养液中分离出来。我们以前从皮肤成纤维细胞培养中分离出一个40 kDa的水蛭素结合蛋白,其氨基酸序列与SSP同源。我们试图澄清SSP和水蛭素结合蛋白之间的关系,如果有的话。我们发现水蛭素结合蛋白与与水蛭素相同的蛋白具有免疫交叉反应。或者非常类似于SSP。这种水蛭素结合蛋白是由培养的正常和类风湿关节炎成纤维细胞以及宫颈癌细胞产生的。一种SSP样蛋白以及大小介于SSP和水蛭素结合蛋白之间的蛋白的痕迹表明,水蛭素结合蛋白可能是由SSP蛋白水解而来的。在所有的滑膜液样本中,无论是关节炎的还是正常的,都存在一种大约200 kDa的ssp样蛋白,这表明它的存在不是类风湿性关节炎的主要原因。没有证据表明滑膜液中存在较小的ssp样蛋白片段。已获得编码部分40kda蛋白的cDNA序列。衍生的氨基酸序列表明,先前在黑腹果蝇的分离基因中发现的结构域存在于该蛋白质中。从cDNA序列中预测的肽段用于培养抗血清,该抗血清可以识别40 kDa蛋白和ssp样蛋白。其中一种抗体制剂是成纤维细胞增殖的良好抑制剂,这证实了这些蛋白最初提出的自分泌生长刺激作用。(C) 2002 Elsevier Science B.V.版权所有
A synovial stimulating protein (SSP) has previously been isolated from rheumatoid arthritis synovial fluid and from the culture fluid of rheumatoid arthritis synovial fibroblasts. We have previously isolated, from skin fibroblast cultures, a 40 kDa hirudin-binding protein, which had amino acid sequence homology with the SSP. We sought to clarify the relationship, if any, between the SSP and the hirudin-binding protein. We show that the hirudin-binding protein is immunologically crossreactive with a protein identical with. or very similar to, the SSP. This hirudin-binding protein is produced by normal and rheumatoid arthritis fibroblasts in culture, and also by cervical carcinoma cells. Traces of an SSP-like protein, and of proteins intermediate in size between the SSP and the hirudin-binding protein, suggest that the hirudin-binding protein may be proteolytically derived from the SSP. An SSP-like protein of about 200 kDa is present in all synovial fluid samples, arthritic and normal, indicating that its presence is not a primary cause of rheumatoid arthritis. There is no evidence for the existence of smaller fragments of the SSP-like protein in synovial fluid. A cDNA sequence, coding for part of the 40 kDa protein, has been obtained. The derived amino acid sequence indicates that a domain, previously identified in the disherelled gene from Drosophila melanogaster, is present in this protein. Peptides predicted from the cDNA sequence were used to raise antisera, which recognise both the 40 kDa protein and the SSP-like protein. One of the antibody preparations is a good inhibitor of fibroblast proliferation, which confirms the autocrine growth-stimulatory role originally proposed for these proteins. (C) 2002 Elsevier Science B.V. All rights reserved.