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Meprins cleave the catalytic subunit of protein kinase A in a meprin isoform‐specific manner
Author(s) -
Ongeri Elimelda Moige,
Ranasinghe Ruvina,
Bond Judith S
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.868.15
Subject(s) - protein kinase a , chemistry , cytosol , protein subunit , kidney , gene isoform , microbiology and biotechnology , metalloproteinase , podocyte , kinase , biochemistry , biology , matrix metalloproteinase , endocrinology , enzyme , gene , proteinuria
Meprins are metalloproteases that are abundantly expressed in the brush border membrane of proximal kidney tubules and small intestines. Meprins are also expressed in podocytes, skin, and leukocytes. Meprins are redistributed to the cytosol after kidney ischemia/reperfusion, and have been implicated in the pathology of diabetic nephropathy (DN). There is increasing knowledge of in vivo kidney meprin substrates, and recently villin and actin were found to be cleaved by meprins. The objective of this study was to determine whether meprins cleave the catalytic subunit of protein kinase A (PKA cat ), and whether the levels of PKA cat are changed in DN. Kidney proteins from meprin αβ double knockout (KO) mice, and purified recombinant human PKA cat were incubated with activated forms of either homomeric meprin A (α‐α) or meprin B (β‐β). The proteins were resolved by SDS‐PAGE and probed by Western blot analysis using PKA cat specific antibodies. Only the meprin B isoform cleaved PKA cat . Cytosolic levels of PKA cat were elevated in kidneys from both WT and meprin KO mice with streptozotocin‐induced type 1 diabetes. Cytosolic PKA cat leveles were higher in WT diabetic kidneys than in meprin double KO diabetic kidneys. The PKA signaling pathway plays a role in glomerular extracellular matrix (ECM) metabolism. Accumulation of ECM proteins is a hallmark of DN, and meprins could modulate the pathology of DN via cleavage of PKA cat .

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