Università della Svizzera italiana

SHP-2 in lymphocytes’ cytokine and inhibitory receptor signaling

Niogret, Charlène ; Birchmeier, Walter ; Guarda, Greta

In: Frontiers in immunology, 2019, vol. 10, no. 2468, p. 1-11

Somewhat counterintuitively, the tyrosine phosphatase SHP-2 (SH2 domain- containing protein tyrosine phosphatase-2) is crucial for the activation of extracellular signal-regulated kinase (ERK) downstream of various growth factor receptors, thereby exerting essential developmental functions. This phosphatase also deploys proto-oncogenic functions and specific inhibitors have recently been ...

Università della Svizzera italiana

Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells

Niogret, Charlène ; Miah, S. M. Shahjahan ; Rota, Giorgia ; Fonta, Nicolas P. ; Wang, Haiping ; Held, Werner ; Birchmeier, Walter ; Sexl, Veronica ; Yang, Wentian ; Vivier, Eric ; Ho, Ping-Chih ; Brossay, Laurent ; Guarda, Greta

In: Nature communications, 2019, vol. 10, p. 1444

The phosphatase Shp-2 was implicated in NK cell development and functions due to its interaction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here we show, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell development and responsiveness are largely unaffected. Instead, we find that Shp-2 serves mainly to enforce NK cell responses to...

Università della Svizzera italiana

Shp-2 is dispensable for establishing T cell exhaustion and for PD-1 signaling in vivo

Rota, Giorgia ; Niogret, Charlène ; Dang, Anh Thu ; Ramon Barros, Cristina ; Fonta, Nicolas Pierre ; Alfei, Francesca ; Morgado, Leonor ; Zehn, Dietmar ; Birchmeier, Walter ; Vivier, Eric ; Guarda, Greta

In: Cell reports, 2018, vol. 23, no. 1, p. 39-49

In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive. To address this, we generated T cell- specific Shp-2-deficient mice. These...