The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3

Mhairi Frame, Kah Fei Wan, R. Tate, Peter Vandenabeele, Nigel J. Pyne

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have investigated whether the proteolysis of members of the cGMP binding phosphodiesterases (PDE6, PDE5A1, and PDE10A2) by caspase-3 is modulated by they inhibitor subunit of PDE6. We show here that purified caspase-3 proteolyses PDE6, an enzyme composed of two nonidentical catalytic subunits (termed alpha and beta) with molecular mass of 88 and 84 kDa. The proteolysis of PDE6 produced a single fragment with a molecular mass of 78 kDa. This corresponds to the possible cleavage of the caspase-3 consensus DFVD site (amino acids: 164-168) in the alpha subunit and leads to a 50% decrease in the cGMP hydrolysing activity of the enzyme. The addition of rod PDE gamma to the incubation completely blocked the cleavage of PDE6 by caspase-3. In contrast, rod PDE gamma converted PDE5A1 (molecular mass of 98 kDa) to a better substrate for caspase-3. This resulted in the formation of four major fragments with molecular mass of 82-83, 67, 43, and 34 kDa. In addition, caspase-3 induced an similar to 80% reduction in the activity of a partially purified preparation of PDE5A1 in the presence of rod PDE gamma. Caspase-3 also cleaved PDE10A2 (molecular mass of 95 kDa) to a single 48-kDa fragment. This was consistent with cleavage of the DLFD site (amino acids: 312-315) in PDE10A2. In contrast with both PDE6 and PDE5A1, rod PDE gamma was without effect on this enzyme. These data show that rod PDE gamma interacts with at least two members of the cGMP binding PDE family (PDE5A1 and PDE6) and can exert differential effects on the cleavage of these enzymes by caspase-3.
Original languageEnglish
Pages (from-to)735-741
Number of pages7
JournalCellular Signalling
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 2001

Keywords

  • PDE gamma
  • cGMP
  • phosphodiesterase
  • lung
  • testes
  • caspases

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