The dual-specific protein tyrosine phosphatase family

Abstract

Dual-specificity protein phosphatases (DSPs) belong to the protein tyrosine phosphatase (PTP) superfamily since they contain the conserved motif HCX2GX2R and share the same tertiary structure. The DSP family constitutes approximately half of all PTPs and includes a diverse group of proteins with a wide distribution among living organisms. They dephosphorylate proteins with phosphate on serine, threonine and/or tyrosine. The best-characterized substrates are the mitogenactivated protein kinases, which are dephosphorylated at tyrosine and threonine in a TXY motif. Additional substrates have been identified recently, ADF/cofilin for the slingshot DSP and glucokinase for DUSP12. DSPs can play key roles in multicellular organisms, as shown for the DSPs puckered and slingshot in the fruit fly and for LIP-1 in the worm. However, the physiological roles that DSPs play in higher vertebrates are largely unknown and there seems to be more redundancy. This chapter will discuss the evolution, structure, and function of the DSP family.