SHP-1 impacts mitochondrial function in cellular metabolism

Abstract

Abstract SHP-1 is a protein tyrosine phosphatase (PTP) that plays critical roles in many hematopoietic cell signaling pathways. For T cells, initial investigations elucidating the role of SHP-1 show its involvement as a negative regulator by dephosphorylating Lck and ZAP70, two kinases instrumental in early T cell activation. Despite its role as a negative regulator, minimal differences were observed in proliferation of SHP-1 −/− CD4 T cells when compared to WT cells. To investigate this disparity metabolism was studied, as cellular division is highly reliant upon energy allocation. Analysis of T cell glycolysis indicated defects in the absence of SHP-1 and that at maximal respiration SHP-1 plays a role in maintaining energy production and is necessary for optimal mitochondria functionality. Furthermore, in the absence of SHP-1 there is approximately 20% reduction in mitochondrial functionality in both naïve and activated CD4 T cells. This goes in parallel with a noted decrease in the amount of ATP in SHP-1 −/− CD4 T cells. Therefore, SHP-1 plays critical roles in T-cell cellular metabolism in addition to being a key regulatory phosphatase.