αB‐Crystallin interacts and attenuates the tyrosine phosphatase activity of Shp2 in cardiomyocytes under mechanical stress

Abstract

The small heat shock protein aB-Crystallin (CryAB, HspB5) and SH2 domain-containing tyrosine phosphatase 2 (Shp2) are important molecules in heart response to pathophysiological stress. Here we show that CryAB interacts with and potentially regulates Shp2 catalytic activity in stretched cardiomyocytes. Such an interaction requires CryAB oligomer to attenuate Shp2 activation. Stretched cardiomyocytes show a robust CryAB/Shp2 association accompanied by a reduction in the Shp2 phosphatase activity. Accordingly, CryAB knock-down in cardiomyocytes enhances Shp2 activity induced by mechanical stress. These results revealed a new role for CryAB, as a modulator of Shp2 phosphatase activity during a functionally relevant stimulus in cardiomyocytes.

The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction

“…Inhibition of CRYAB leads to a decrease in endogenous VEGF levels, providing clear evidence that targeting CRYAB may represent a novel approach to suppress angiogenesis. It should be noted that CRYAB is also expressed at high levels in the the heart and cardiomyocytes, conferring protection against stress (such as an ischaemic event) by inhibiting apoptosis (Pereira et al 2014;Gonçalves et al 2016;Morrison et al 2003). Therefore, direct inhibition of CRYAB could lead to unwanted cardiotoxicity.…”