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Induction of a Nerve Growth Factor‐Sensitive Kinase that Phosphorylates the DNA‐Binding Domain of the Orphan Nuclear Receptor NGFI‐B
Author(s) -
Hirata Yoko,
Whalin Michael,
Ginty David D.,
Xing Jun,
Greenberg Michael E.,
Milbrandt Jeffrey,
Guroff Gordon
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65041780.x
Subject(s) - map2k7 , map kinase kinase kinase , mitogen activated protein kinase kinase , cyclin dependent kinase 9 , protein kinase a , cyclin dependent kinase 2 , phosphorylation , microbiology and biotechnology , biology , c raf , ask1 , chemistry , biochemistry
Nerve growth factor (NGF) induces the synthesis and the phosphorylation of the orphan nuclear receptor NGFI‐B in PC12 cells. Previous work has shown that phosphorylation, by protein kinase A, of a specific serine in the DNA‐binding domain inhibits its binding to the NGFI‐B response element. Also, cytoplasmic extracts from PC12 cells phosphorylate this serine, and phosphorylation is greater in extracts from cells treated with NGF. The present work describes the induction, identification, and partial purification of a kinase (termed NGFI‐B kinase I) from PC12 cell extracts that catalyzes this phosphorylation. Phosphorylation of the DNA‐binding domain with this purified preparation inhibits its binding to the NGFI‐B response element. The kinase is rapidly activated by treatment of the cells with NGF, and the activation lasts for at least several hours. It also is activated by fibroblast growth factor and epidermal growth factor (EGF), but the activation by EGF is quite transient. The kinase requires Mg 2+ but will use Mn 2+ . The molecular mass of the kinase is 95–100 kDa, and it is different from protein kinase A, Fos kinase, or pp90 rsk . Comparison with a partially purified preparation of cyclic AMP response element‐binding protein kinase, however, indicates that the two are either very similar or identical.