WD40 repeat proteins striatin and S/G(2) nuclear autoantigen are members of a novel family of calmodulin-binding proteins that associate with protein phosphatase 2A.
Protein phosphatase 2A (PP2A) is a multifunctional serine/threonine phosphatase that is critical to many cellular processes including development, neuronal signaling, cell cycle regulation, and viral transformation. PP2A has been implicated in Ca(2+)-dependent signaling pathways, but how PP2A is targeted to these pathways is not understood. We have identified two calmodulin (CaM)-binding proteins that form stable complexes with the PP2A A/C heterodimer and may represent a novel family of PP2A B-type subunits. These two proteins, striatin and S/G(2) nuclear autoantigen (SG2NA), are highly related WD40 repeat proteins of previously unknown function and distinct subcellular localizations. Striatin has been reported to associate with the post-synaptic densities of neurons, whereas SG2NA has been reported to be a nuclear protein expressed primarily during the S and G(2) phases of the cell cycle. We show that SG2NA, like striatin, binds to CaM in a Ca(2+)-dependent manner. In addition to CaM and PP2A, several unidentified proteins stably associate with the striatin-PP2A and SG2NA-PP2A complexes. Thus, one mechanism of targeting and organizing PP2A with components of Ca(2+)-dependent signaling pathways may be through the molecular scaffolding proteins striatin and SG2NA.
Moreno
C S
CS
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Park
S
S
Nelson
K
K
Ashby
D
D
Hubalek
F
F
Lane
W S
WS
Pallas
D C
DC
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D000939:Epitopes; D006657:Histones / Q000378:metabolism; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry*; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D054648:Protein Phosphatase 2; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D001324:Autoantigens; D002148:Calmodulin-Binding Proteins; D000939:Epitopes; D006657:Histones; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491925:STRN protein, human; C491924:Strn protein, mouse; C485775:Strn3 protein, mouse; C485774:Strn3 protein, rat; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D002118:Calcium