SARP, a new alternatively spliced protein phosphatase 1 and DNA interacting protein

Gareth J. Browne , Margarida Fardilha , Senga K. Oxenham , Wenjuan Wu , Nicholas R. Helps , Odete A.B. da Cruz E Silva , Patricia T.W. Cohen (1) , Edgar F. da Cruz E Silva

1 MRC Protein Phosphorylation Unit

Protein phosphatase 1 (PP1) is a ubiquitously expressed serine/threonine-specific protein phosphatase whose activity towards different substrates appears to be mediated via binding to specific proteins that play critical regulatory and targeting roles. We report here the cloning and characterization of a new protein, termed several ankyrin repeat protein (SARP), which is shown to interact with all isoforms of PP1 by a variety of techniques. A region encompassing a consensus PP1 binding motif in SARP ( 354}KVHF 357}) modulates endogenous SARP-PP1 activity in mammalian cells. This SARP PP1 interaction motif lies partially within the first ankyrin repeat in contrast to other proteins (53BP2, MYPT1/ M 110}//MBS and TIMAP) where a PP1 binding motif precedes the ankyrin repeats. Alternative mRNA splicing produces several isoforms of SARP from a single human gene at locus 11q14. SARP1 and/or SARP2 (92-95 kDa) are ubiquitously expressed in all tissues with high levels in testis and sperm, where they are shown to interact with both PP1 γ1} and PP1 γ2}. SARP3 (65 kDa) is most abundant in brain where SARP isoforms interact with both PP1 α} and PP1 γ1}. SARP is highly abundant in the nucleus of mammalian cells, consistent with the putative nuclear localisation signal at the N-terminus. The presence of a leucine zipper near the C-terminus of SARP1 and SARP2, and the binding of mammalian DNA to SARP2, suggests that SARP1 and SARP2 may be transcription factors or DNA associated proteins that modulate gene expression

Mots clés: Life Sciences

Gareth J. Browne, Margarida Fardilha, Senga K. Oxenham, Wenjuan Wu, Nicholas R. Helps, et al.. SARP, a new alternatively spliced protein phosphatase 1 and DNA interacting protein. Biochemical Journal, 2006, 402 (1), pp.187-196. ⟨10.1042/BJ20060600⟩. ⟨hal-00478582⟩