THE FEATURES AND ROLE OF SHP2 PROTEIN IN POSTNATAL MUSCLE DEVELOPMENT

Abstract

SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with carry germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities.Shp2 is an important signaling agent for growth factors and cytokines. To investigate the Ptpn11 in postnatal myogenesis of mice  we analyzed using immunohistochemistry stem cell markers: Pax 7, Myo D, Myf 5 and Myo G in muscle cells isolated from wild type and Shp2 knockout mice. We used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Our findings indicate that all these markers gradually decreased from birth to day 14 in mouse muscle cells. Here we show that Shp2, an intracellular tyrosine phosphatase with two SH2 domains, plays a critical role in mouse muscle development after birth. Our data demonstrate a molecular difference in the control and Sh2 knockout  postnatal myogenic stem cells, and assign to Ptpn11 signaling a key function in satellite cell activity. These findings illustrate an essential role for Shp-2 in muscle growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how Shp-2 regulates muscle morphogenesis, which could lead to the development of novel therapies for the treatment of malformations in human patients with SHP-2 mutations.