Phosphorylation of the skeletal muscle AMP‐deaminase by protein kinase C

Tovmasian, E.K.; Hairapetian, R.L.; Быкова, Е. В.; Severin, S E; Haroutunian, A. V.

doi:10.1016/0014-5793(90)80037-j

Cited by 22 publications

(9 citation statements)

References 13 publications

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“…Therefore, its phosphorylation can be seen as a preventive action against the possible inhibition coming from the increasing lactate concentration; obviously muscle cells lose this preventing ability when ATP concentration is strongly reduced, clearly from day 10 onward. AMP-deaminase undergoes a phosphorylative regulatory modification which boosts its enzymatic activity [52] at days 0 and 1 (Fig. 4).…”

Section: Energetic Evolutionmentioning

confidence: 99%

Apoptosis in muscle-to-meat aging process: The omic witness

Longo

Lana

Bottero

et al. 2015

Journal of Proteomics

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Section: Energetic Evolutionmentioning

confidence: 99%

Apoptosis in muscle-to-meat aging process: The omic witness

Longo

Lana

Bottero

et al. 2015

Journal of Proteomics

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“…The AMPD1 isoform is found almost exclusively in skeletal muscle, whereas the AMPD2 and AMPD3 isoforms are widely expressed in many tissues and cells (19,20), including mammalian brain (21,22). AMPD activity is highly regulated through interactions with other proteins (23)(24)(25), phosphorylation (26,27), and small molecules (10, 11, 28 -32). Regarding the latter, polyphosphates (32) and inositol (1,2,3,4,5,6)-hexakisphosphate (10) inhibit AMPD, whereas inositol (1,3,4,5)-tetrakisphosphate (Ins(1,3,4,5)P 4 ) modestly stimulates AMPD activity (11).…”

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confidence: 99%

Regulation of AMP Deaminase by Phosphoinositides

Sims

Mahnke-Zizelman

Profit

et al. 1999

Journal of Biological Chemistry

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AMP deaminase (AMPD) converts AMP to IMP and is a diverse and highly regulated enzyme that is a key component of the adenylate catabolic pathway. In this report, we identify the high affinity interaction between AMPD and phosphoinositides as a mechanism for regulation of this enzyme. We demonstrate that endogenous rat brain AMPD and the human AMPD3 recombinant enzymes specifically bind inositide-based affinity probes and to mixed lipid micelles that contain phosphatidylinositol 4,5-bisphosphate. Moreover, we show that phosphoinositides specifically inhibit AMPD catalytic activity. Phosphatidylinositol 4,5-bisphosphate is the most potent inhibitor, effecting pure noncompetitive inhibition of the wild type human AMPD3 recombinant enzyme with a K i of 110 nM. AMPD activity can be released from membrane fractions by in vitro treatment with neomycin, a phosphoinositide-binding drug. In addition, in vivo modulation of phosphoinositide levels leads to a change in the soluble and membrane-associated pools of AMPD activity. The predicted human AMPD3 sequence contains pleckstrin homology domains and (R/ K)X n (R/K)XKK sequences, both of which are characterized phosphoinositide-binding motifs. The interaction between AMPD and phosphoinositides may mediate membrane localization of the enzyme and function to modulate catalytic activity in vivo.Phosphoinositides and inositol polyphosphates (referred to collectively as inositides) are components of many pathways in eukaryotic cells, functioning in second messenger cascades, acting as regulators of many proteins, and operating as membrane localization signals (1-3). Numerous protein and lipid kinases, adaptor proteins, ion channels, phospholipases, modulators of small GTPases, and actin-binding proteins are regulated by inositides (1-3). To identify novel targets for inositides, our laboratories and others have used purification schemes employing affinity resins that contain tethered inositol polyphosphate head groups (3-9). These affinity purifications were successful in the identification of inositide binding in the clathrin adaptor/assembly protein AP-2 (6), centaurin ␣ (7), a centaurin ␣ orthologue (8), and a phospholipase C (PLC) 1 -related protein (9). In addition to AP-2 and centaurin ␣, we isolated several other proteins from rat brain, one of which was approximately 80 kDa (5). Published reports show that inositol polyphosphates modulate the activity of the enzyme AMP deaminase (EC 3.5.4.6) (AMPD) (10, 11), an enzyme family whose endogenous, purified subunit molecular masses are between 66 and 88 kDa. Therefore, we hypothesized that AMPD could be the 80-kDa protein isolated using the inositide affinity resin.AMPD is a diverse and highly regulated enzyme located at a branchpoint in the adenine nucleotide catabolic pathway and is important in regulating nucleotide pools. AMPD is also a component of the purine nucleotide cycle, an energy-generating pathway reportedly operative in many animal tissues (reviewed in Ref. 12). The AMPD1 gene encodes human isoform M and rat iso...

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“…Rat skeletal-muscle AMP deaminase has been reported to serve as a PKC substrate, its apparent Km decreasing from 0.6 mM AMP to 0.2 mM AMP upon phosphorylation [29]. Thus the Km of 1.2 mM for cardiac phospho-AMP deaminase indicates that PKC-dependent phosphorylation brings its substrate affinity near the 0.3-0.7 mM Km range reported for various skeletalmuscle AMP deaminase isoforms [30,31].…”

Section: Discussionmentioning

confidence: 92%

Modulation of mammalian cardiac AMP deaminase by protein kinase C-mediated phosphorylation

Thakkar¹,

Janero²,

Yarwood³

et al. 1993

Biochemical Journal

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Using AMP deaminase (AMP aminohydrolase; EC 3.5.4.6) purified from rabbit left-ventricular heart tissue, we report direct investigation of the potential for cardiac AMP deaminase activity to be regulated by kinase-mediated phosphorylation. Rabbit heart AMP deaminase served as a substrate for Ca2+/phospholipid-dependent protein kinase (protein kinase C; PKC) exclusively; no other mammalian protein kinase phosphorylated the enzyme. PKC-dependent AMP deaminase phosphorylation was rapid, linear with respect to time and the concentrations of PKC and AMP deaminase in the reaction, and inhibitable by staurosporine. Upon phosphorylation, the apparent Km of cardiac AMP deaminase decreased from 5.6 mM to 1.2 mM, without effect on the Vmax. Whether phosphorylated or not, rabbit heart AMP deaminase was inhibited by 1.0 mM GTP, which decreased the Vmax. by approximately 50% in each case. PKC-dependent phosphorylation of cardiac AMP deaminase did not alter the enzyme's allosterism toward millimolar ATP or ADP: both nucleotides at 1.0 mM concentration decreased the apparent Km to approximately 0.5 mM. Treatment of cardiac phospho-AMP deaminase with either the protein phosphatase calcineurin or alkaline phosphatase generated a dephosphorylated form which displayed molecular and kinetic properties identical with those of the originally isolated enzyme. These data raise the possibility that a phosphorylation-dephosphorylation mechanism may regulate flux through AMP deaminase in the heart under pathological conditions, such as myocardial ischaemia, characterized by PKC activation and adenylate depletion.

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Phosphorylation of the skeletal muscle AMP‐deaminase by protein kinase C

Cited by 22 publications

References 13 publications

Apoptosis in muscle-to-meat aging process: The omic witness

Apoptosis in muscle-to-meat aging process: The omic witness

Regulation of AMP Deaminase by Phosphoinositides

Modulation of mammalian cardiac AMP deaminase by protein kinase C-mediated phosphorylation

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