Protein Kinase CK2 Is Inhibited by Human Nucleolar Phosphoprotein p140 in an Inositol Hexakisphosphate-dependent Manner

Yun-Kyoung Kim,Hyesung Jeon,Kong Joo Lee,Yeon Gyu Yu

doi:10.1074/jbc.m604785200

Abstract

Protein kinase CK2 is a ubiquitous protein kinase that can phosphorylate various proteins involved in central cellular processes, such as signal transduction, cell division, and proliferation. We have shown that the human nucleolar phosphoprotein p140 (hNopp140) is able to regulate the catalytic activity of CK2. Unphosphorylated hNopp140 and phospho-hNopp140 bind to the regulatory and catalytic subunits of CK2, respectively, and the interaction between hNopp140 and CK2 was prevented by inositol hexakisphosphate (InsP(6)). Phosphorylation of alpha-casein, genimin, or human phosphatidylcholine transfer protein-like protein by CK2 was inhibited by hNopp140, and InsP(6) recovered the suppressed activity of CK2 by hNopp140. These observations indicated that hNopp140 serves as a negative regulator of CK2 and that InsP(6) stimulates the activity of CK2 by blocking the interaction between hNopp140 and CK2.

Highlights

The protein kinase CK2, formerly known as casein kinase II, is a serine/threonine protein kinase that has been found in virtually all tissues and cell lines and is responsible for the phosphorylation of more than 300 cellular proteins [1]
We have shown that the human nucleolar phosphoprotein p140 is able to regulate the catalytic activity of CK2
The cellular function of CK2 is related to essential processes such as cell cycle, proliferation, or signal transduction since the proteins phosphorylated by CK2 are involved in DNA replication and transcription, translation, and signal transduction [2,3,4,5]

Summary

Introduction

The protein kinase CK2, formerly known as casein kinase II, is a serine/threonine protein kinase that has been found in virtually all tissues and cell lines and is responsible for the phosphorylation of more than 300 cellular proteins [1]. These observations indicated that hNopp140 serves as a negative regulator of CK2 and that InsP6 stimulates the activity of CK2 by blocking the interaction between hNopp140 and CK2. Because hNopp140 is highly phosphorylated in cell extracts [26], hNopp140 would normally bind to the catalytic subunit of CK2 and repress its catalytic activity.

Results

Conclusion