Studies on insulin-stimulated phosphorylation of acetyl-CoA carboxylase, ATP citrate lyase and other proteins in rat epididymal adipose tissue. Evidence for activation of a cyclic AMP-independent protein kinase

Brownsey, Roger W.; Edgell, N J; Hopkirk, T J; Denton, R M

doi:10.1042/bj2180733

Cited by 56 publications

(34 citation statements)

References 57 publications

(41 reference statements)

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“…Interestingly, the pattern of phosphorylation observed using the anti-PKB substrate antibody was very similar to the pattern of 32 P-labeled phosphoproteins observed after insulin stimulation of primary rat adipocytes metabolically labeled with [ 32 P]P i (21,22). This suggests that this antibody recognizes the majority of the most abundant insulin-stimulated phosphoproteins in rat fat cells.…”

Section: Insulin-stimulated Protein Phosphorylation In Primary Ratsupporting

confidence: 51%

The Identification of ATP-citrate Lyase as a Protein Kinase B (Akt) Substrate in Primary Adipocytes

Berwick¹,

Hers²,

Heesom³

et al. 2002

Journal of Biological Chemistry

328

279

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Protein kinase B (Akt) plays a central role in cellular regulation, although many of the physiologically relevant substrates for the kinase remain to be identified. In this study, we have isolated a protein from primary epididymal adipocytes with an apparent molecular weight of 125,000. This protein exhibited immunoreactivity, in an insulin-dependent manner, with a phosphospecific antibody raised against the protein kinase B substrate consensus sequence RXRXX(pS/pT) as well as a phosphospecific antibody that recognizes serine 21/9 of GSK-3␣/␤. MALDI-TOF mass spectrometry revealed the protein to be ATP-citrate lyase, suggesting that the two phosphospecific antibodies recognize phosphoserine 454, a previously reported insulin-and isoproterenolstimulated ATP-citrate lyase phosphorylation site. Indeed, both insulin and isoproterenol stimulated the phosphorylation of this protein on the site recognized by the phosphospecific antibodies in a wortmannin-sensitive and -insensitive manner, respectively. In addition, transient expression of a constitutively active protein kinase B in primary adipocytes mimicked the effect of insulin on ATP-citrate lyase phosphorylation. Furthermore, ATP-citrate lyase was phosphorylated in vitro by recombinant protein kinase B on the same site. Taken together, these results demonstrate that serine 454 of ATP-citrate lyase is a novel and major in vivo substrate for protein kinase B.

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Section: Insulin-stimulated Protein Phosphorylation In Primary Ratsupporting

confidence: 51%

The Identification of ATP-citrate Lyase as a Protein Kinase B (Akt) Substrate in Primary Adipocytes

Berwick¹,

Hers²,

Heesom³

et al. 2002

Journal of Biological Chemistry

328

279

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“…Insulin reverses the inhibition caused by AMPK in hepatoma and heart cells [48], although this effect has not been observed in primary fat or liver cells and appears to be independent of changes in concentration of cAMP or 5 -AMP. In fact, full activation of ACC-1 is also accompanied by 'increased' phosphorylation by an insulinactivated protein kinase [49]. Like other metabolic effects, the activation of ACC by insulin is blocked by inhibition of the PI3K (phosphoinositide 3-kinase) signalling pathway, but the relevant 'ACC kinase' has not been identified [50].…”

Section: Differential Control Of Acc-1 and Acc-2 By Multiple-site Phomentioning

confidence: 99%

Regulation of acetyl-CoA carboxylase

Brownsey¹,

Boone²,

Elliott³

et al. 2006

Biochem. Soc. Trans

168

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Acetyl-CoA carboxylase (ACC) catalyses the formation of malonyl-CoA, an essential substrate for fatty acid synthesis in lipogenic tissues and a key regulatory molecule in muscle, brain and other tissues. ACC contributes importantly to the overall control of energy metabolism and has provided an important model to explore mechanisms of enzyme control and hormone action. Mammalian ACCs are multifunctional dimeric proteins (530-560 kDa) with the potential to further polymerize and engage in multiprotein complexes. The enzymatic properties of ACC are complex, especially considering the two active sites, essential catalytic biotin, the three-substrate reaction and effects of allosteric ligands. The expression of the two major isoforms and splice variants of mammalian ACC is tissue-specific and responsive to hormones and nutritional status. Key regulatory elements and cognate transcription factors are still being defined. ACC specific activity is also rapidly modulated, being increased in response to insulin and decreased following exposure of cells to catabolic hormones or environmental stress. The acute control of ACC activity is the product of integrated changes in substrate supply, allosteric ligands, the phosphorylation of multiple serine residues and interactions with other proteins. This review traces the path and implications of studies initiated with Dick Denton in Bristol in the late 1970s, through to current proteomic and other approaches that have been consistently challenging and immensely rewarding.

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“…For example insulin is known to stimulate the serine (occasionally threonine) phosphorylation of a whole range of cellular substrates, including acetyl-CoA carboxylase, ATP citrate lyase, ribosomal protein S6, cyclic AMP phosphodiesterase and several unidentified proteins (Denton et al, 1981;Marchmont & Houslay, 1981;Avruch et al, 1985). These effects of insulin involve activation of the serine kinases (Brownsey et al, 1984), although the actual kinases are poorly characterized. Interestingly, in intact cells phosphorylation on serine residues of the /3-subunit of the insulin receptor itself is increased by insulin (Gazzano et al, 1983;Takayama et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Evidence that a novel serine kinase catalyses phosphorylation of the insulin receptor in an insulin-dependent and tyrosine kinase-dependent manner

Smith

Sale

1988

Biochemical Journal

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Insulin receptor was co-purified from human placenta together with insulin-stimulated kinase activity that phosphorylates the insulin receptor on serine residues. By using this 'in vitro' system, the mechanism of activation of the serine kinase by insulin was explored. Peptide 1150, histone, poly(Glu-Tyr), eliminating Mn2+ (Mg2" only), treatment at 37°C (1 h), N-ethylmaleimide, phosphate, /3-glycerol phosphate and antiphosphotyrosine antibody all inhibited insulin-receptor tyrosine kinase activity and the ability of insulin to stimulate phosphorylation of the insulin receptor on serine. Additionally, direct stimulation of the receptor tyrosine kinase by vanadate increased serine phosphorylation of the insulin receptor. Insulin-stimulated tyrosine phosphorylation preceded insulin-stimulated serine phosphorylation of the insulin receptor. The activity of the insulin-sensitive receptor serine kinase was not augmented by cyclic AMP, cyclic GMP, Ca2", Ca2++calmodulin, Ca2++phosphatidylserine+diolein or spermine, or inhibited appreciably by heparin. Additionally, the serine kinase phosphorylated casein or phosvitin poorly and was active with Mn2". This indicates that it is distinct from Ca2 , Ca2 /phospholipid, Ca2 /calmodulin, cyclic AMP-and cyclic GMP-dependent protein kinases, casein kinases I and II and insulin-activated ribosomal S6 kinase. Taken together, these data indicate that a novel species of serine kinase catalyses the insulin-dependent phosphorylation of the insulin receptor and that activation of this receptor serine kinase by insulin requires an active insulin-receptor tyrosine kinase. INTRODUCTIONThe insulin receptor is an insulin-activated tyrosinespecific protein kinase which catalyses the autophos-

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Studies on insulin-stimulated phosphorylation of acetyl-CoA carboxylase, ATP citrate lyase and other proteins in rat epididymal adipose tissue. Evidence for activation of a cyclic AMP-independent protein kinase

Cited by 56 publications

References 57 publications

The Identification of ATP-citrate Lyase as a Protein Kinase B (Akt) Substrate in Primary Adipocytes

The Identification of ATP-citrate Lyase as a Protein Kinase B (Akt) Substrate in Primary Adipocytes

Regulation of acetyl-CoA carboxylase

Evidence that a novel serine kinase catalyses phosphorylation of the insulin receptor in an insulin-dependent and tyrosine kinase-dependent manner

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