Localization of Src Homology 2 Domain-Containing Phosphatase 1 (SHP-1) to Lipid Rafts in T Lymphocytes: Functional Implications and a Role for the SHP-1 Carboxyl Terminus

摘要: The protein tyrosine phosphatase Src homology 2 domain-containing 1 (SHP-1) has previously been shown to be a negative regulator of signaling mediated via the TCR. A growing body evidence indicates that regulated localization proteins within certain membrane subdomains, referred as lipid rafts, is important for successful transduction events downstream However, considerably less known about regulators during these raft-dependent events. In this study we have investigated subcellular SHP-1 and its role in regulation TCR-mediated signaling. Our studies demonstrate murine T cell hybridoma well primary thymocytes, fraction localizes both basally after TCR stimulation. Interestingly, although localized nonraft fractions phosphorylated, isolated from rafts lacks TCR-induced phosphorylation, suggesting physical and/or functional differences between two subpopulations. We identify requirement C-terminal residues optimal rafts. Although expression potently inhibits early IL-2 production, raft-excluded mutants fails elicit any inhibitory effects. Taken together reveal key raft mediating effects on