Identification, characterization, and intracellular processing of ADAM-TS12, a novel human disintegrin with a complex structural organization involving multiple thrombospondin-1 repeats.
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| Abstract |
We have identified and cloned a human fetal lung cDNA encoding a new protein of the ADAM-TS family (a disintegrin and metalloproteinase domain, with thrombospondin type-1 modules) that has been called ADAM-TS12. This protein exhibits a domain organization similar to the remaining family members including a propeptide and metalloproteinase-like, disintegrin-like, and cysteine-rich domains. However, the number and organization of the TS repeats is unique with respect to other human ADAM-TSs. A total of eight TS-1 repeats arranged in three groups are present in this novel ADAM-TS. Analysis of intracellular processing of ADAM-TS12 revealed that it is synthesized as a precursor molecule that is first activated by cleavage of the prodomain in a furin-mediated process and subsequently processed into two fragments of different size: a 120-kDa N-terminal proteolytically active fragment containing the metalloproteinase and disintegrin domains, and a 83-kDa C-terminal fragment containing most of the TS-1 repeats. Somatic cell hybrid and radiation hybrid mapping experiments showed that the human ADAM-TS12 gene maps to 5q35, a location that differs from all ADAM genes mapped to date. Northern blot analysis of RNAs from human adult and fetal tissues demonstrated that ADAM-TS12 transcripts are only detected at significant levels in fetal lung but not in any other analyzed tissues. In addition, ADAM-TS12 transcripts were detected in gastric carcinomas and in tumor cell lines from diverse sources, being induced by transforming growth factor-beta in KMST human fibroblasts. These data suggest that ADAM-TS12 may play roles in pulmonary cells during fetal development or in tumor processes through its proteolytic activity or as a molecule potentially involved in regulation of cell adhesion.
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| Authors | S Cal, J M Arguelles, P L Fernandez, C López-Otín |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 21 Pg. 17932-40 (May 25 2001) ISSN: 0021-9258 [Print] United States |
| PMID | 11279086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication) |
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