Phosphorylation of D‐glyceraldehyde‐3‐phosphate dehydrogenase by Ca<sup>2+</sup>/calmodulin‐dependent protein kinase II

Ashmarina, L.I.; Louzenko, Serguei E.; Severin, S E; Muronetz, Vladimir I.; Nagradova, N.K.

doi:10.1016/0014-5793(88)80861-5

Cited by 22 publications

(14 citation statements)

References 16 publications

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“…Considering the basic change in pI, it may be reasonable to suggest phosphorylation as this post-translational modification. This would be in accord with previously described GAPDH phosphorylation by protein kinases [Reiss et al, 1986;Ashmarina et al, 1988;Tisdale, 2002] or by its autophosphorylation [Kawamoto and Caswell, 1986]. Irrespective of the specific post-translational modification, a further support for this control mechanism is the defined cell cycle regulation of GAPDH subcellular localization defined in these new studies (Table I) and in previous investigations [Schmitz, 2001;Corbin Gong et al, 2002].…”

Section: Discussionsupporting

confidence: 83%

New nuclear functions of the glycolytic protein, glyceraldehyde‐3‐phosphate dehydrogenase, in mammalian cells

Sirover

2005

J of Cellular Biochemistry

294

229

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Recent studies establish that the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is not simply a classical metabolic protein involved in energy production. Instead, it is a multifunctional protein with defined functions in numerous subcellular processes. New investigations establish a primary role for GAPDH in a variety of critical nuclear pathways apart from its already recognized role in apoptosis. These new roles include its requirement for transcriptional control of histone gene expression, its essential function in nuclear membrane fusion, its necessity for the recognition of fraudulently incorporated nucleotides in DNA, and its mandatory participation in the maintenance of telomere structure. Each of these new functions requires GAPDH association into a series of multienzyme complexes. Although other proteins in those complexes are variable, GAPDH remains the single constant protein in each structure. To undertake these new functions, GAPDH is recruited to the nucleus in S phase or its intracellular distribution is regulated as a function of drug exposure. Other investigations relate a substantial role for nuclear GAPDH in hyperglycemic stress and the development of metabolic syndrome. Considerations of future directions as well as the role of GAPDH post-translational modification as a basis for its multifunctional activities is suggested.

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Section: Discussionsupporting

confidence: 83%

New nuclear functions of the glycolytic protein, glyceraldehyde‐3‐phosphate dehydrogenase, in mammalian cells

Sirover

2005

J of Cellular Biochemistry

294

229

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“…Our observation that GAPDH is an in situ substrate for PhK was not completely surprising, given that once before it had been reported that under unspecified in vitro conditions a small amount of phosphate was incorporated into purified GAPDH by PhK (48). Prior to that, the EGF receptor tyrosine kinase had been shown to phosphorylate GAPDH in vitro to relatively high yields (49).…”

Section: Discussionmentioning

confidence: 96%

The Regulatory β Subunit of Phosphorylase Kinase Interacts with Glyceraldehyde-3-phosphate Dehydrogenase

et al. 2008

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Skeletal muscle phosphorylase kinase (PhK) is an (αβγδ) 4 hetero-oligomeric enzyme complex that phosphorylates and activates glycogen phosphorylase b (GPb) in a Ca 2+ -dependent reaction that couples muscle contraction with glycogen breakdown. GPb is PhK's only known in vivo substrate; however, given the great size and multiple subunits of the PhK complex, we screened muscle extracts for other potential targets. Extracts of P/J (control) and I/lnJ (PhK deficient) mice were incubated with [γ-32 P]ATP with or without Ca 2+ and compared to identify potential substrates. Candidate targets were resolved by two-dimensional polyacrylamide gel electrophoresis, and phosphorylated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified by matrix-assisted laser desorption ionization mass spectroscopy. In vitro studies showed GAPDH to be a Ca 2+ -dependent substrate of PhK, although the rate of phosphorylation is very slow. GAPDH does, however, bind tightly to PhK, inhibiting at low concentrations (IC 50 0 .45 µM) PhK's conversion of GPb. When a short synthetic peptide substrate was substituted for GPb, the inhibition was negligible, suggesting that GAPDH may inhibit predominantly by binding to the PhK complex at a locus distinct from its active site on the γ subunit. To test this notion, the PhK-GAPDH complex was incubated with a chemical cross-linker, and a dimer between the regulatory β subunit of PhK and GAPDH was formed. This interaction was confirmed by the fact that a subcomplex of PhK missing the β subunit, specifically an αγδ subcomplex, was unable to phosphorylate GAPDH, even though it is catalytically active toward GPb. Moreover, GAPDH had no effect on the conversion of GPb by the αγδ subcomplex. The interactions described herein between the β subunit of PhK and GAPDH provide a possible mechanism for the direct linkage of glycogenolysis and glycolysis in skeletal muscle.Phosphorylase kinase (ATP:phosphorylase b phosphotransferase, EC 2.7.1.38), hereafter termed PhK, 1 is in fast-twitch skeletal muscle a hexadecameric complex with a subunit composition of (αβγδ) 4 and a mass of 1.3 × 10 6 Da (reviewed in ref 1). The activity of its catalytic γ subunit (44.7 kDa) is controlled by its regulatory α (138.4 kDa), β (125.2 kDa),

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“…It is possible that either site or both can be phosphorylated also by other kinases such as casein kinase II or Ca 2ϩ / camodulin-dependent protein kinase II (34,35), although the exact amino acid modified by them is unknown. Nonetheless, Thr-246 substituted by alanine (T246A) was sufficient to abolish PKC␦-mediated inhibition of mitophagy during I/R-induced injury, which coincided with a reduction in mitochondrial mass.…”

Section: Discussionmentioning

confidence: 99%

Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Phosphorylation by Protein Kinase Cδ (PKCδ) Inhibits Mitochondria Elimination by Lysosomal-like Structures following Ischemia and Reoxygenation-induced Injury

Yogalingam¹,

Hwang²,

Ferreira³

et al. 2013

Journal of Biological Chemistry

102

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Background: How damaged mitochondria are removed by mitophagy is not fully described. Results: Ischemia and reoxygenation (I/R)-induced injury triggers mitochondria association of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and mitophagy, and protein kinase C␦ (PKC␦) activation inhibits it. Conclusion: PKC␦-mediated phosphorylation of GAPDH inhibits mitophagy. Significance: GAPDH/PKC␦ is a signaling switch, which is activated during ischemic injury to regulate the balance between cell survival by mitophagy and cell death by apoptosis.

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Phosphorylation of D‐glyceraldehyde‐3‐phosphate dehydrogenase by Ca²⁺/calmodulin‐dependent protein kinase II

Cited by 22 publications

References 16 publications

New nuclear functions of the glycolytic protein, glyceraldehyde‐3‐phosphate dehydrogenase, in mammalian cells

New nuclear functions of the glycolytic protein, glyceraldehyde‐3‐phosphate dehydrogenase, in mammalian cells

The Regulatory β Subunit of Phosphorylase Kinase Interacts with Glyceraldehyde-3-phosphate Dehydrogenase

Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Phosphorylation by Protein Kinase Cδ (PKCδ) Inhibits Mitochondria Elimination by Lysosomal-like Structures following Ischemia and Reoxygenation-induced Injury

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Phosphorylation of D‐glyceraldehyde‐3‐phosphate dehydrogenase by Ca2+/calmodulin‐dependent protein kinase II

Cited by 22 publications

References 16 publications

New nuclear functions of the glycolytic protein, glyceraldehyde‐3‐phosphate dehydrogenase, in mammalian cells

New nuclear functions of the glycolytic protein, glyceraldehyde‐3‐phosphate dehydrogenase, in mammalian cells

The Regulatory β Subunit of Phosphorylase Kinase Interacts with Glyceraldehyde-3-phosphate Dehydrogenase

Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Phosphorylation by Protein Kinase Cδ (PKCδ) Inhibits Mitochondria Elimination by Lysosomal-like Structures following Ischemia and Reoxygenation-induced Injury

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Phosphorylation of D‐glyceraldehyde‐3‐phosphate dehydrogenase by Ca²⁺/calmodulin‐dependent protein kinase II