Hsp70 associates with Rictor and is required for mTORC2 formation and activity

Martin, Jheralyn; Masri, Janine; Bernath, Andrew; Nishimura, Robert N.; Gera, Joseph

doi:10.1016/j.bbrc.2008.05.086

Cited by 67 publications

(52 citation statements)

References 34 publications

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“…The expression of Hsp70 is significantly associated with the amount of ATP in cells. The expression of Hsp70 is inhibited by the high levels of ATP; however, ATP depletion markedly induced the expression of Hsp70 (Arispe et al 2002;Martin et al 2008). Simmons et al (2005) and Selak et al (2003) have confirmed that mitochondrial ATP production was impaired in islets and muscle of IUGR rat, respectively.…”

Section: Discussionmentioning

confidence: 79%

Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets

Zhong

Wang

Zhang

et al. 2010

Cell Stress and Chaperones

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The objective of this study is to investigate the expression and distribution of heat shock protein 70 (Hsp70) in the intestine of intrauterine growth retardation (IUGR) piglets. Samples from the duodenum, prejejunum, distal jejunum, ileum, and colon of IUGR and normalbody-weight (NBW) piglets were collected at birth. The results indicated that the body and intestine weight of IUGR piglets were significantly lower than NBW piglets. The villus height and villus/crypt ratio in jejunum and ileum of IUGR piglets were significantly reduced compared to NBW piglets. These results indicated that IUGR causes abnormal gastrointestinal morphologies and gastrointestinal dysfunction. The mRNA of hsp70 was increased in prejejunum (P<0.05), distal jejunum (P<0.05), and colon in IUGR piglets. However, the hsp70 mRNA in ileum of piglets with IUGR was decreased. Similar to hsp70 mRNA, the protein levels of Hsp70 in prejejunum (P<0.05), distal jejunum, and colon (P<0.05) in IUGR piglets were higher than those in NBW piglets. These results indicated that the expression of Hsp70 in the intestinal piglets was upregulated by IUGR, and different intestinal sites had different responses to stress. Meanwhile, the localization of Hsp70 in the epithelial cells of the whole villi and intestinal gland rather than in the lamina propria and myenteron suggested that Hsp70 has a cytoprotective role in epithelial cell function and structure.

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Section: Discussionmentioning

confidence: 79%

Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets

Zhong

Wang

Zhang

et al. 2010

Cell Stress and Chaperones

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“…Recently, it has been shown that Hsp72 is identified as a rictorbinding protein and a component of the mammalian target of rapamycin complex 2. 24 Activation of mammalian target of rapamycin complex 2, which consists of rictor, leads to the phosphorylation of Akt at Ser473, resulting in full activation of Akt. 25 Thus, the observation that Hsp70s regulate kinase function is not unique.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Cognate Protein 70 Is Essential for Akt Signaling in Endothelial Function

Shiota

Kusakabe

Izumi

et al. 2010

ATVB

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Objective-Heat shock protein 70s (Hsp70s) are molecular chaperones that protect cells from damage in response to various stress stimuli. However, the functions and mechanisms in endothelial cells (ECs) have not been examined. Herein, we investigate the role of Hsp70s, including heat shock cognate protein 70 (Hsc70), which is constitutively expressed in nonstressed cells (ie, ECs). Hsp72, a member of the Hsp70 family, protects cells, tissues, and organs from various harmful conditions in blood vessels. Previous work 4,5 has shown that an increase in levels of a particular Hsp72, induced by heat stress, is associated with the protection of ventricular and endothelial function after ischemia-reperfusion injury. Several studies 6 -9 have been reported that upregulation of Hsp72 in cells by gene transfer greatly increases the resistance of myocardial cells in vitro and in transgenic mice. On the other hand, deletion of Hsp72 leads to dysfunctional cardiomyocytes and impaired stress response of Hsp72-knockout hearts against ischemia/ reperfusion. 10 Thus, Hsp72 may be expected to play a protective role by reducing the risk of myocardial cell injury and exerting its beneficial effects on endothelial function. However, little is known about the functional role of Hsp70 family members in response to ischemic injury. Methods and Results-TheThe human Hsp70 family, which is the largest and most conserved Hsp family, contains at least eight homologous chaperone proteins. This family includes the Hsp72-inducible protein and constitutively expresses the heat shock cognate protein 70 (Hsc70) isoform, both of which are localized to the cytoplasm. Two members of the Hsp70 family, Hsc70 and Hsp72, have a high degree of sequence homology (86% sequence identity), and both proteins copurify with one another. Hsc70 is abundantly and ubiquitously expressed in all cells, whereas Hsp72 is expressed only at low levels in most unstressed healthy cells and tissues. However, its expression is rapidly induced by a variety of physical and chemical stresses; therefore, it is often called the major stress-inducible Hsp70. It is suggested that Hsp72 and Hsc70 can substitute for each other in healthy cells, whereas Hsp72 expression is essential for certain cells to respond to some cytotoxic factors. There are several chaperone mechanisms based on inducible Hsp72 and constitutive Hsc70. Although both bind to misfolded proteins, newly synthesized polypeptides (ie, Hsp72 and Hsc70) function in the cytosol, suggesting that they display specificity for their client proteins or, alternatively, serve particular chaperone-independent functions. 11 Previous studies mainly analyzed Hsp72 under vari- ous stress conditions; however, there is little research on Hsc70 in the cardiovascular system. In the present study, we investigated whether Hsp70s modulate the angiogenic process. Recently, it has been reported that RNAi-mediated knockdown of human Hsc 70 A12B, a member of the Hsp70 family, disrupted normal zebra fish blood vessel development and inhibited in ...

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“…Hsp70 family proteins are highly conserved and have three regions mediating interaction with various proteins, including an ATPase domain in the N-terminal region, a peptide binding domain in the C-terminal region, and an acidic motif (EEVD) at the C terminus. The peptide binding domain of Hsp70 has been reported to bind to PKC␤II, p53, Rictor, apoptosis-inducing factor (AIF), JNK1, TRAF2, TRAF6, Ku70, and MstI (7,11,16,29,37,40,54,58,59). Meanwhile, Hsp70 interacts with Hip, Bag-1, Bax, hYVH1, PARP-1, CD40, and Ask1 via its ATPase domain (3,17,25,26,36,53,64) and with Hop (Hsp70/Hsp90-organizing protein) and CHIP via the EEVD motif (1,12).…”

Section: Discussionmentioning

confidence: 99%

The Ras Signaling Inhibitor LOX-PP Interacts with Hsp70 and c-Raf To Reduce Erk Activation and Transformed Phenotype of Breast Cancer Cells

Sato

Trackman

Mäki

et al. 2011

Molecular and Cellular Biology

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Hsp70 associates with Rictor and is required for mTORC2 formation and activity

Cited by 67 publications

References 34 publications

Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets

Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets

Heat Shock Cognate Protein 70 Is Essential for Akt Signaling in Endothelial Function

The Ras Signaling Inhibitor LOX-PP Interacts with Hsp70 and c-Raf To Reduce Erk Activation and Transformed Phenotype of Breast Cancer Cells

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