Deletion of ribosomal S6 kinases does not attenuate pathological, physiological, or insulin-like growth factor 1 receptor-phosphoinositide 3-kinase-induced cardiac hypertrophy
Authors: Adam L Dorfman
Oleg Tarnavski
Li Zhang
Seigo Izumo
George Thomas
Sarah Longnus
Tetsuo Shioi
Mario Pende
Kathleen A Martin
Julie R McMullen
John Blenis
Megan C Sherwood
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ribosomal S6 kinases; protein synthesis; cardiac hypertrophy; growth factor pathways; insulin-like growth factor 1
Affiliations: Beth Israel Deaconess Medical Center, Cardiovascular Division, 330 Brookline Ave., SL-408, Boston, MA 02215, USA. , Beth Israel Deaconess Medical Center, Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland, Department of Cell Biology, Harvard Medical School

Abstract:  Ribosomal S6 kinases (S6Ks) have been depicted as critical effectors downstream of growth factor pathways, which play an important role in the regulation of protein synthesis by phosphorylating the ribosomal protein, S6. The goal of this study was to determine whether S6Ks regulate heart size, are critical for the induction of cardiac hypertrophy in response to a pathological or physiological stimulus, and whether S6Ks are critical downstream effectors of the insulin-like growth factor 1 (IGF1)-phosphoinositide 3-kinase (PI3K) pathway. For this purpose, we generated and characterized cardiac-specific S6K1 and S6K2 transgenic mice and subjected S6K1(-/-), S6K2(-/-), and S6K1(-/-) S6K2(-/-) mice to a pathological stress (aortic banding) or a physiological stress (exercise training). To determine the genetic relationship between S6Ks and the IGF1-PI3K pathway, S6K transgenic and knockout mice were crossed with cardiac-specific transgenic mice overexpressing the IGF1 receptor (IGF1R) or PI3K mutants. Here we show that overexpression of S6K1 induced a modest degree of hypertrophy, whereas overexpression of S6K2 resulted in no obvious cardiac phenotype. Unexpectedly, deletion of S6K1 and S6K2 had no impact on the development of pathological, physiological, or IGF1R-PI3K-induced cardiac hypertrophy. These studies suggest that S6Ks alone are not essential for the development of cardiac hypertrophy. 

Retracted: No

PubPeer comments:
 Fig. 7. b) Ex-situ XRD patterns of NiHCF RGO in different selected states. Unexpected similarities.  , 
 #1 Hello, thank you very much for your question. Fig. 7b is the ex-situ XRD test of the same electrode we selected in different charging and discharging states. Based on your comment, we are also curious about the similarity of some parts of the graphs. To clarify this issue, we have checked the data and found they are correct. In fact, when we re-processed the data with a thinner brush to draw the profiles, it can be clearly seen that there are some differences between the curves. Thank you again for your comments!    , 
 #2 Dear author, Looking at figure 7(b) I can only come to one conclusion: in the left part of panel (b) the a- and f-curves are duplicates, and in the right part of the b- and f- curves are duplicates. Also, the a- and b-curves are switched in the left panel. I am a bit worried by you showing that the curves are not exactly identical in your reply. Shot noise is fundamentally random in nature and seeing your very high frequency (in 2theta) noise mostly but not completely reproduce is, well, puzzling. What is in your opinion the physical origin of the high frequency peaks ( 0.02 degree wide) in the spectrum you are showing? , 
 Unfortunately, the curve cannot match (a and b) in Fig. 7b.  , 
 Dear sir madam: Thank you very much for your valuable comments. Based on your comment, I demanded the first author to carefully compare and verify all the original data, and found that due to his negligence in the data processing, the data in the state a and the state f in Figure 7b overlapped during the drawing. In addition, the order of curves a and b in the two enlarged parts on the right has also been reversed. Here, I sincerely apologize for the mistakes. We have contacted the Editor of the journal to correct the mistakes. Great thanks to you for helping us find this problem. ,