PITK, a PP1 targeting subunit that modulates the phosphorylation of the transcriptional regulator hnRNP K.

Published

Journal Article

Protein phosphatase-1 (PP1), through interactions with substrate targeting subunits, plays critical roles in the regulation of numerous cellular processes. Herein, we describe a newly identified regulatory subunit (PITK; Phosphatase Interactor Targeting K protein) that specifically targets the catalytic subunit of PP1 to nuclear foci to selectively bind and dephosphorylate the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K) at a regulatory S284 site. Additionally, PITK is phosphorylated in vivo at S1013 and S1017, residues that flank or reside within the PP1C-binding motif, and this phosphorylation negatively regulates the binding of the phosphatase to PITK. A mutant variant, S1013,1017A-PITK, when expressed in intact cells, exhibited an increase in native PP1 binding and elicited a more profound dephosphorylation of hnRNPK at S284. A global analysis of transcription by Affymetrix microarray revealed that the expression of PITK resulted in the altered expression of 47 genes, including a marked induction of MEK5 (>14-fold, p<0.007). Additionally, the effects of PITK and S1013,1017A-PITK on transcription could be modulated by the co-expression of hnRNP K. Taken together, our findings provide a putative mechanism by which transcriptional activity of hnRNP K can be discretely controlled through the regulation of PP1 activity.

Full Text

Duke Authors

Cited Authors

  • Kwiek, NC; Thacker, DF; Datto, MB; Megosh, HB; Haystead, TAJ

Published Date

  • October 2006

Published In

Volume / Issue

  • 18 / 10

Start / End Page

  • 1769 - 1778

PubMed ID

  • 16564677

Pubmed Central ID

  • 16564677

Electronic International Standard Serial Number (EISSN)

  • 1873-3913

International Standard Serial Number (ISSN)

  • 0898-6568

Digital Object Identifier (DOI)

  • 10.1016/j.cellsig.2006.01.019

Language

  • eng