Activation of the Jnk signaling pathway by a dual-specificity phosphatase,JSP-1

The mitogen-activated protein kinases (MAPKs) are integral to the mechanism s by which cells respond to physiological stimuli, such as growth factors, hormones, and cytokines, and to a wide variety of environmental stresses. T he MAPKs, which are stimulated by phosphorylation of a TXY motif in their a ctivation loop, are components of signal transduction cascades in which seq uential activation of protein kinases culminates in their activation and th eir subsequent phosphorylation of various effector proteins that mediate th e physiological response. MAPKs are also subject to dephosphorylation and i nactivation, both by enzymes that recognize the residues of the TXY motif i ndependently and by dual specificity phosphatases, which dephosphroylate bo th Tyr and Ser/Thr residues. We report the identification and characterizat ion of a novel dual specificity phosphatase. Contrary to expectation, this broadly expressed enzyme did not inactivate MAPKs in transient cotransfecti on assays but instead displayed the capacity to function as a selective act ivator of the MAPK ink, hence the name, Jnk Stimulatory Phosphatase-1 (JSP- 1). This study illustrates a new aspect of the regulation of MAPK-dependent signal transduction and raises the possibility that JSP-1 may offer a diff erent perspective to the study of various inflammatory and proliferative di sorders associated with dysfunctional ink signaling.