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Regulation of the Nuclear Protein Kinase CK1αLS by Mitogenic Levels of Hydrogen Peroxide
Author(s) -
Stone James R.,
Bedri Shahinaz,
Cizek Stephanie M.,
Rastarhuyeva Iryna
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a181
Subject(s) - dephosphorylation , kinase , protein kinase a , phosphatase , chemistry , phosphorylation , alkaline phosphatase , biochemistry , microbiology and biotechnology , biology , enzyme
Low physiologic concentrations of H 2 O 2 stimulate vascular cell proliferation and play an important role in the proliferative phases of human vascular diseases. The biochemical mechanisms whereby human vascular cells sense and respond to these low levels of H 2 O 2 remain poorly understood. Low concentrations of H 2 O 2 have been shown to stimulate the rapid hyperphosphorylation of the nuclear pre‐mRNA binding protein hnRNP‐C by protein kinase CK1α. Here it is shown that application of low concentrations of H 2 O 2 to endothelial cells increases the isoelectric point of protein kinase CK1αLS, the nuclear splice form of CK1α. An identical change is accomplished by treating nuclear extracts with alkaline phosphatase in vitro, indicating that H 2 O 2 is stimulating the dephosphorylation of the kinase. This dephosphorylation is maximal with 5 μM H 2 O 2 , and occurs prior to hnRNP‐C hyperphosphorylation. Treatment of endothelial cells with H 2 O 2 stimulates the association of CK1αLS with hnRNP‐C. Likewise, treating CK1αLS with alkaline phosphatase in vitro also stimulates the association of the kinase with hnRNP‐C, indicating that association of the kinase with its substrate is facilitated by dephosphorylation.