ERK is a novel regulatory kinase for poly(A) polymerase.
Poly(A) polymerase (PAP), which adds poly(A) tails to the 3' end of mRNA, can be phosphorylated at several sites in the C-terminal domain. Phosphorylation often mediates regulation by extracellular stimuli, suggesting PAP may be regulated by such stimuli. In this study, we found that phosphorylation of PAP was increased upon growth stimulation and that the mitogen-activated protein kinase ERK was responsible for the increase in phosphorylation. We identified serine 537 of PAP as a unique phosphorylation site by ERK. PAP phosphorylation of serine 537 by ERK increased its nonspecific polyadenylation activity in vitro. This PAP activity was also activated by stimulation of ERK with phorbol-12-myristate-13-acetate in vivo. These data suggest that ERK is a novel regulatory kinase for PAP and further, that PAP activity could be regulated by extracellular stimuli through an ERK-dependent signaling pathway(s).
Lee
Seol-Hoon
SH
Department of Chemistry and Center for Molecular Design and Synthesis, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Choi
Hyun-Sook
HS
Kim
Hana
H
Lee
Younghoon
Y
D000818:Animals; D045163:Antibodies, Phospho-Specific; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010768:Phosphoserine / Q000032:analysis / Q000276:immunology; D011062:Polynucleotide Adenylyltransferase / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D045163:Antibodies, Phospho-Specific; D010768:Phosphoserine; D048049:Extracellular Signal-Regulated MAP Kinases; D011062:Polynucleotide Adenylyltransferase