Role of tyrosine phosphorylation in the regulation of cleavage secretion of angiotensin-converting enzyme.

The Journal of Biological Chemistry
K R SanthammaIndira Sen

Abstract

Both germinal (gACE) and somatic (sACE) isozymes of angiotensin-converting enzyme (ACE) are type I ectoproteins whose enzymatically active ectodomains are cleaved and shed by a membrane-bound protease. Here, we report a role of protein tyrosine phosphorylation in regulating this process. Strong enhancements of ACE cleavage secretion was observed upon enhancing protein Tyr phosphorylation by treating gACE- or sACE-expressing cells with pervanadate, an inhibitor of protein Tyr phosphatases. Secreted gACE, cell-bound mature gACE and its precursors were all Tyr-phosphorylated, as was the endoplasmic reticulum protein, immunoglobulin heavy chain-binding protein, that co-immunoprecipitated with ACE. The enhancement of cleavage secretion by pervanadate did not require the presence of the cytoplasmic domain of ACE, and it was not accomplished by enhancing the rate of intracellular processing of the protein. The observed enhancement of cleavage secretion of ACE in pervanadate-treated cells was specifically blocked by an inhibitor of the p38 mitogen-activated protein (MAP) kinase but not by inhibitors of many other Ser/Thr and Tyr protein kinases, including a specific inhibitor of protein kinase C that, however, could block the enhanceme...Continue Reading

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Citations

Aug 6, 2008·Cardiovascular Drugs and Therapy·Kenji IizukaMasahiko Hirafuji
Aug 24, 2010·Omics : a Journal of Integrative Biology·Guang-Rong YanQing-Yu He
May 27, 2010·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Kazutaka HayashidaPyong Woo Park
Apr 15, 2006·Circulation Research·Ingrid Fleming
Dec 1, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sean P KesslerGanes C Sen

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