Evidence for participation of transglutaminase in receptor-mediated endocytosis.
- 1 May 1980
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 77 (5), 2706-2710
- https://doi.org/10.1073/pnas.77.5.2706
Abstract
Evidence is reported that the enzyme transglutaminase (EC 2.3.2.13) participates in receptor-mediated endocytosis. Clustering and internalization of rhodamine-labeled .alpha.2-macroglobulin (R.alpha.2M) in normal rat kidney (NRK) cells is inhibited by a wide spectrum of compounds that inhibit transglutaminases, including that from NRK cells. The pattern of clustering inhibition resembles the pattern of transglutaminase inhibition. The most potent transglutaminase inhibitors are dansylcadaverine and the transglutaminase-directed affinity label N-benzyloxycarbonyl-5-diazo-4-oxonorvaline p-nitrophenyl ester; these were the most potent inhibitors of clustering and internalization of R.alpha.2M. The inhibition of clustering of R.alpha.2M occurs in the same concentration range as that required for transglutaminase inhibition. Linear primary amines are more effective blockers than the iso-chain primary amines. The transglutaminase affinity label N-benzyloxycarbonyl-5-diazo-4-oxonorvaline p-nitrophenyl ester irreversibly inhibits a significant fraction of the NRK transglutaminase and the clustering and internalization of Ra2M. A closely related compound, N-trifluoroacetyl-6-diazo-5-oxonorleucine ethyl ester, does not significantly inhibit transglutaminase or clustering and internalization. Clustering and internalization are inhibited 10-fold more effectively be the heptapeptide Ac-Gly2-LLeu-LLys-Gly3 than by the heptapeptides Ac-Gly2-LLeu-DLys-Gly3 or Ac-Gly3-DLys-DLeu-Gly2. This is the pattern of stereospecificity for the inhibition of purified transglutaminases.This publication has 19 references indexed in Scilit:
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