Abstract
It has generally been considered that protein phosphatases have more diverse catalytic domain structures and mechanisms than protein kinases; however, gene annotation efforts following the human genome project appeared to have completed the whole array of protein phosphatases. Ser/Thr phosphatases are divided into three subfamilies that have different structures from each other, whereas Tyr phosphatases and dual-specificity phosphatases targeting Tyr, Ser and Thr belong to a single large family based on their common structural features. Several years of research have revealed, however, the existence of unexpected proteins, designated here as “atypical protein phosphatases”, that have structural and enzymatic features different from those of the known protein phosphatases and are involved in important biological processes. In this review, we focus on the identification and functional characterization of atypical protein phosphatases, represented by eyes absent (EYA), suppressor of T-cell receptor signaling (Sts) and phosphoglycerate mutase family member 5 (PGAM5) and discuss their biological significance in cellular signaling.
Highlights
Protein kinases have highly conserved catalytic domain structures, irrespective of their substrate specificity, and all protein kinases were annotated relatively soon after the human genome project was completed [1]
EYA4-deficient mice exhibit severe hearing deficits and develop otitis media with effusion [12], which may resemble the effects of the EYA4 mutations, which cause sensorineural hearing loss accompanied by cardiomyopathy in humans [13,14,15,16]
Hyperresponsiveness of suppressor of T-cell receptor signaling (Sts)-1/2-deficient T-cells was reduced by reconstitution of the wild-type Suppressor of T-cell receptor signaling-1 (Sts-1), but not by a mutant Sts-1 in which the catalytic His was substituted by Ala. These findings demonstrate that the phosphatase activity of Sts-1 plays a critical role in the control of T-cell antigen receptor (TCR) signaling
Summary
Protein kinases have highly conserved catalytic domain structures, irrespective of their substrate specificity, and all protein kinases were annotated relatively soon after the human genome project was completed [1]. Tyr phosphatases and dual-specificity phosphatases targeting Tyr, Ser and Thr constitute a single large family based on their common structural features. These proteins use an essential Cys residue as a nucleophile that forms a thiol-phosphate intermediate during catalysis [4]. Ser/Thr phosphatases are divided into three subfamilies that have different structures, the phosphoprotein phosphatase (PPP) and metal-dependent protein phosphatase (PPM) metalloenzyme families and the TFIIF-associating component of RNA polymerase II carboxy-terminal domain phosphatase (FCP). Tyr phosphatase; LMPTP, low molecular weight PTP; VH1-like DSP, Vaccinia virus gene H1-like dual-specificity phosphatase; PPP, phosphoprotein phosphatase; PPM, metal-dependent protein phosphatase; FCP, TFIIF-associating component of RNA polymerase II carboxy-terminal domain phosphatase
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
