The positive and negative control actions of PTPase on IL-2 signaling.
The tyrosine phosphorylation of intracellular proteins was greatly increased after the treatment of cells with sodium n-vanadate, the inhibitor of protein tyrosine phosphatase (PTPase). It was found by using EMSA that during this period the signal transducer and activator of transcription 5 (STAT5) were tyrosine-phosphorylated and activated STAT5 may bind to v-interferon activated sequence (GAS). Contrast to the activation of STAT5 by interleukin-2 (IL-2), the activation for STATS by sodium n-vanadate cannot be completely blocked by the inhibitor of protein tyrosine kinase (PTK). In addition, sodium n-vanadate may augment the IL-2 up-regulation on the expression of reporter genes containing GAS in their promoter regions. All the results here show that PTPase may negatively regulate the JAK-STAT signal transduction pathway induced by IL-2. However, the inhibition of PTPase activity may block the induction of tnf-beta gene and c-myc gene transcription by IL-2 and ultimately results in cell death. Therefore, PTPase plays positive or negative control roles on different signaling pathways induced by IL-2. Both actions of PTPase are offered through its phosphatase activity.
Zhu
J
J
Shanghai Institute of Biochemistry, Chinese Academy of Sciences, China.
Ji
H
H
Lu
L
L
Guo
L
L
Zheng
Z
Z
Liu
X
X