Interaction of heavy chain binding protein (BiP/GRP78) with adenine nucleotides.

Kassenbrock, C. Kenneth; Kelly, Regis B.

doi:10.1002/j.1460-2075.1989.tb03529.x

Cited by 179 publications

(166 citation statements)

References 23 publications

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“…The in vivo functions of both proteins are dependent on an inherent ATPase activity and phosphorylation (24,25,38,39). Conditions giving rise to increased levels and activity of GRP78 are followed by a decreased phosphorylation of GRP78 (25), whereas phosphorylation of HSP 90 seems to be linked to its chaperoning function (24).…”

Section: Table III Sum Of Expression Of Protein Markers Isoformsmentioning

confidence: 99%

Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes

Højlund

Wrzesinski

Larsen

et al. 2003

Journal of Biological Chemistry

209

156

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Insulin resistance in skeletal muscle is a hallmark feature of type 2 diabetes. An increasing number of enzymes and metabolic pathways have been implicated in the development of insulin resistance. However, the primary cellular cause of insulin resistance remains uncertain. Proteome analysis can quantitate a large number of proteins and their post-translational modifications simultaneously and is a powerful tool to study polygenic diseases like type 2 diabetes. Using this approach on human skeletal muscle biopsies, we have identified eight potential protein markers for type 2 diabetes in the fasting state. The observed changes in protein expression indicate increased cellular stress, e.g. up-regulation of two heat shock proteins, and perturbations in ATP (re)synthesis and mitochondrial metabolism, e.g. down-regulation of ATP synthase ␤-subunit and creatine kinase B, in skeletal muscle of patients with type 2 diabetes. Phosphorylation appears to play a key, potentially coordinating role for most of the proteins identified in this study. In particular, we demonstrated that the catalytic ␤-subunit of ATP synthase is phosphorylated in vivo and that the levels of a down-regulated ATP synthase ␤-subunit phosphoisoform in diabetic muscle correlated inversely with fasting plasma glucose levels. These data suggest a role for phosphorylation of ATP synthase ␤-subunit in the regulation of ATP synthesis and that alterations in the regulation of ATP synthesis and cellular stress proteins may contribute to the pathogenesis of type 2 diabetes.Insulin resistance in skeletal muscle, defined as reduced insulin-stimulated glucose disposal, is a characteristic feature of type 2 diabetes mellitus (T2DM) 1 and is believed to be largely accounted for by reduced non-oxidative glucose metabolism (1-3). Furthermore, insulin stimulation of glucose oxidation and suppression of lipid oxidation is significantly impaired in patients with T2DM (2, 3). Conversely, in the basal, fasting state increased glucose oxidation and reduced lipid oxidation is seen in skeletal muscle of insulin resistant subjects, whether caused by T2DM or obesity alone (4). These defects suggest an impaired capacity to switch between carbohydrate and fat as oxidative energy sources in insulin-resistant subjects. Together with reports of reduced oxidative enzyme activity and dysfunction of mitochondria in skeletal muscle of patients with T2DM (4 -6) and the fact that mitochondrial DNA defects cause T2DM through impairment of oxidative phosphorylation (7, 8), these abnormalities in fuel metabolism have led to the hypotheses that perturbations in skeletal muscle mitochondrial metabolism (6, 9, 10) and defects in the signaling pathways of AMP-activated protein kinase (AMPK) are implicated in the pathogenesis of T2DM (11). That rates of fuel oxidation and mitochondrial function can affect glucose uptake and glycogen synthesis has been reported earlier (12, 13). In addition, both chronic activation of AMPK and induced expression of the transcriptional co-activator of peroxisom...

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Section: Table III Sum Of Expression Of Protein Markers Isoformsmentioning

confidence: 99%

Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes

Højlund

Wrzesinski

Larsen

et al. 2003

Journal of Biological Chemistry

209

156

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“…Recently, decreased protease sensitivity of BiP was observed after adding adenine nucleotides like ATP and ADP, but not after adding nonhydrolyzable ATP analogues. This may point to a role of the nucleotides in stabilization or induction of different conformations of BiP in the absence of ATP hydrolysis (KASSENBROCK and KELLY 1989). Furthermore, covalent modifications of hsp70 proteins, such as ADP ribosylation, methylation at lysine and arginine residues, or phosphorylation at serine and threonine residues, may be involved in the regulation of their function (WANG and LAZARIDES 1984;HENDERSHOT et al 1988).…”

Section: Physiological Functions Of Hsp70 Proteinsmentioning

confidence: 99%

“…BiP possesses a peptide-dependent ATPase activity (KASSENBROCK and KELLY 1989;FLYNN et al 1989) characterized by a low turnover number and a high affinity for ATP. The decreased sensitivity of BiP to proteolytic degradation in the presence of ATP or ADP suggests that adenine nucleotides may stabilize special conformations of BiP (KASSENBROCK and KELLY 1989).…”

Section: Bip-the Hsp70 Homologue In the Endoplasmic Reticulummentioning

confidence: 99%

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Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Langer¹,

Neupert²

1991

Current Topics in Microbiology and Immunology

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“…BiP function may be regulated by calcium (Kassenbrock and Kelly, 1989) and BiP has also been implicated in ER calcium storage (Lievremont et al, 1997). Possible roles for calcium in glycoprotein folding are discussed below.…”

Section: Bipmentioning

confidence: 99%

Glycoprotein Folding in the Endoplasmic Reticulum

Benham

Braakman

2000

Critical Reviews in Biochemistry and Molecular Biology

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Our understanding of eukaryotic protein folding in the endoplasmic reticulum has increased enormously over the last 5 years. In this review, we summarize some of the major research themes that have captivated researchers in this field during the last years of the 20th century. We follow the path of a typical protein as it emerges from the ribosome and enters the reticular environment. While many of these events are shared between different polypeptide chains, we highlight some of the numerous differences between proteins, between cell types, and between the chaperones utilized by different ER glycoproteins. Finally, we consider the likely advances in this field as the new century unfolds and we address the prospect of a unified understanding of how protein folding, degradation, and translation are coordinated within a cell.

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Interaction of heavy chain binding protein (BiP/GRP78) with adenine nucleotides.

Cited by 179 publications

References 23 publications

Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes

Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes

Heat Shock Proteins hsp60 and hsp70: Their Roles in Folding, Assembly and Membrane Translocation of Proteins

Glycoprotein Folding in the Endoplasmic Reticulum

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