Protein-Serine-Threonine Kinases

Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

Activation of adenosine monophosphate-activated protein kinase (AMPK) plays a central role in allowing cells to adapt to nutrient deprivation in vitro. This link between AMPK activity and nutritional status has raised the possibility that AMPK plays a role in the metabolic adaptation to acute and chronic nutritional stress. However, the effects of nutritional stress on AMPK activity in vivo have not been systematically evaluated.

Gonzalez, Asensio A.
Kumar, Reetu
Mulligan, Jacob D.
Davis, Ashley J.
Weindruch, Richard
Saupe, Kurt W.
Publication Title: 
Cancer Research

Dietary energy restriction (DER) is a potent inhibitor of carcinogenesis, but chronic DER in human populations is difficult to sustain. Consequently, interest exists in identifying energy restriction mimetic agents (ERMAs), agents that provide the health benefits of DER without reducing caloric intake. The selection of a candidate ERMAs for this study was based on evidence that DER inhibits carcinogenesis by limiting glucose availability. The study objective was to determine if 2-deoxyglucose (2-DG), a glucose analogue that blocks its metabolism, would inhibit mammary carcinogenesis.

Zhu, Zongjian
Jiang, Weiqin
McGinley, John N.
Thompson, Henry J.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Resveratrol is a polyphenol produced by plants that has multiple beneficial activities similar to those associated with caloric restriction (CR), such as increased life span and delay in the onset of diseases associated with aging. CR improves neuronal health, and the global beneficial effects of CR have been postulated to be mediated by the nervous system. One key enzyme thought to be activated during CR is the AMP-activated kinase (AMPK), a sensor of cellular energy levels.

Dasgupta, Biplab
Milbrandt, Jeffrey
Publication Title: 
FASEB journal: official publication of the Federation of American Societies for Experimental Biology

Energy conservation directed at accelerating body fat recovery (or catch-up fat) contributes to obesity relapse after slimming and to excess fat gain during catch-up growth after malnutrition.

Summermatter, S.
Mainieri, D.
Russell, A. P.
Seydoux, J.
Montani, J. P.
Buchala, A.
Solinas, G.
Dulloo, A. G.
Publication Title: 
Current Opinion in Pharmacology

The dynamic regulation of the structure, function and turnover of mitochondria is recognized as an immutable control node maintaining cellular integrity and homeostasis. The term 'mitohormesis' has recently been coined to describe the adaptive reprogramming of mitochondrial biology in response to low levels of metabolic substrate deprivation to augment subsequent mitochondrial and cellular tolerance to biological stress.

Schwartz, Daniel R.
Sack, Michael N.
Publication Title: 
Neurobiology of Aging

The aging program mediated by IGF1-R is responsible for a naturally occurring TrkA to p75(NTR) switch that leads to activation of the second messenger ceramide and increased production of the Alzheimer's disease amyloid beta-peptide. Biochemical and genetic approaches that target IGF1-R signaling, p75(NTR), or ceramide are able to block the above events. Here, we show that the transcription factors Egr-1 and Hipk2 are required elements for the TrkA to p75(NTR) switch downstream of IGF1-R signaling.

Li, Hui
Costantini, Claudio
Scrable, Heidi
Weindruch, Richard
Puglielli, Luigi
Publication Title: 

Acetylation of histone and nonhistone proteins is an important posttranslational modification affecting many cellular processes. Here, we report that NuA4 acetylation of Sip2, a regulatory β subunit of the Snf1 complex (yeast AMP-activated protein kinase), decreases as cells age. Sip2 acetylation, controlled by antagonizing NuA4 acetyltransferase and Rpd3 deacetylase, enhances interaction with Snf1, the catalytic subunit of Snf1 complex.

Lu, Jin-Ying
Lin, Yu-Yi
Sheu, Jin-Chuan
Wu, June-Tai
Lee, Fang-Jen
Chen, Yue
Lin, Min-I.
Chiang, Fu-Tien
Tai, Tong-Yuan
Berger, Shelley L.
Zhao, Yingming
Tsai, Keh-Sung
Zhu, Heng
Chuang, Lee-Ming
Boeke, Jef D.
Publication Title: 
PLoS genetics

Knowledge of the mechanisms for regulating lifespan is advancing rapidly, but lifespan is a complex phenotype and new features are likely to be identified. Here we reveal a novel approach for regulating lifespan. Using a genetic or a pharmacological strategy to lower the rate of sphingolipid synthesis, we show that Saccharomyces cerevisiae cells live longer. The longer lifespan is due in part to a reduction in Sch9 protein kinase activity and a consequent reduction in chromosomal mutations and rearrangements and increased stress resistance.

Huang, Xinhe
Liu, Jun
Dickson, Robert C.
Publication Title: 
World journal of gastroenterology: WJG

AIM: The transforming growth factor-beta (TGF-beta)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver fibrogenesis. Smad proteins can either positively or negatively regulate TGF-beta responses. In this study, the therapeutic effects of Chinese traditional compound decoction, JinSanE, and the changes of TGF-beta/Smad signaling pathway system in carbon tetrachloride (CCl(4))-induced rat experimental liver fibrosis were examined.

Song, Shi-Ling
Gong, Zuo-Jiong
Zhang, Quan-Rong
Huang, Tuan-Xin
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

During kidney organogenesis, tubular epithelial cells proliferate until a functional tubule is formed as sensed by cilia bending in response to fluid flow. This flow-induced ciliary mechanosensation opens the calcium (Ca(2+)) channel polycystin-2 (PC2), resulting in a calcium flux-mediated cell cycle arrest. Loss or mutation of either PC2 or its regulatory protein polycystin-1 (PC1) results in autosomal dominant polycystic kidney disease (ADPKD), characterized by cyst formation and growth and often leading to renal failure and death.

Leuenroth, Stephanie J.
Okuhara, Dayne
Shotwell, Joseph D.
Markowitz, Glen S.
Yu, Zhiheng
Somlo, Stefan
Crews, Craig M.


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