Int J Biol Sci 2008; 4(3):184-199. doi:10.7150/ijbs.4.184 This issue Cite

Research Paper

STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX

Christopher D. Willey1,*, Arun P. Palanisamy1,*, Rebecca K. Johnston1, Santhosh K. Mani1, Hirokazu Shiraishi1, William J. Tuxworth1, Michael R. Zile1,2, Sundaravadivel Balasubramanian1, Dhandapani Kuppuswamy1,2

1. Cardiology Division of the Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, SC 29425-2221, USA
2. Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC 29425-2221, USA
* Both authors contributed equally to this work

Citation:
Willey CD, Palanisamy AP, Johnston RK, Mani SK, Shiraishi H, Tuxworth WJ, Zile MR, Balasubramanian S, Kuppuswamy D. STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX. Int J Biol Sci 2008; 4(3):184-199. doi:10.7150/ijbs.4.184. https://www.ijbs.com/v04p0184.htm
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Abstract

Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival.

Keywords: STAT3, BMX, integrin, pressure-overload, cardiac hypertrophy


Citation styles

APA
Willey, C.D., Palanisamy, A.P., Johnston, R.K., Mani, S.K., Shiraishi, H., Tuxworth, W.J., Zile, M.R., Balasubramanian, S., Kuppuswamy, D. (2008). STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX. International Journal of Biological Sciences, 4(3), 184-199. https://doi.org/10.7150/ijbs.4.184.

ACS
Willey, C.D.; Palanisamy, A.P.; Johnston, R.K.; Mani, S.K.; Shiraishi, H.; Tuxworth, W.J.; Zile, M.R.; Balasubramanian, S.; Kuppuswamy, D. STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX. Int. J. Biol. Sci. 2008, 4 (3), 184-199. DOI: 10.7150/ijbs.4.184.

NLM
Willey CD, Palanisamy AP, Johnston RK, Mani SK, Shiraishi H, Tuxworth WJ, Zile MR, Balasubramanian S, Kuppuswamy D. STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX. Int J Biol Sci 2008; 4(3):184-199. doi:10.7150/ijbs.4.184. https://www.ijbs.com/v04p0184.htm

CSE
Willey CD, Palanisamy AP, Johnston RK, Mani SK, Shiraishi H, Tuxworth WJ, Zile MR, Balasubramanian S, Kuppuswamy D. 2008. STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX. Int J Biol Sci. 4(3):184-199.

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