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PMID: 7925294 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A mitogen- and anisomycin-stimulated kinase phosphorylates HMG-14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes.

The EMBO journal ·Vol. 13 ·No. 19 ·1994-10-03 ·Pages 4524-35

Barratt MJ, Hazzalin CA, Zhelev N, Mahadevan LC

Abstract

The rapid, transient induction of 80-100 immediate-early (IE) genes upon mitogenic stimulation occurs irrespective of protein synthesis and is mediated by modification of existing proteins. Two mechanisms, not mutually exclusive, involving modification either of sequence-specific transcription factors or of structural chromatin proteins primed by pre-association with responsive effectors are conceivable. Here, we show that upon IE gene induction, the non-histone high-mobility-group protein HMG-14, but not the related protein HMG-17, becomes serine phosphorylated in its basic, amino-terminal region close to where it binds nucleosomal DNA. Phosphorylation, normally transient, occurs independent of transcription and is quantitative and prolonged during superinduction. Brief micrococcal nuclease digestion substantially releases HMG-14 from nuclei in the mononucleosome-bound state. Finally, mononucleosomes prepared from mitogen-stimulated, but not control, cells contain a mitogen-activated kinase that phosphorylates HMG-14 in vitro on the same site(s) as in intact cells. The association of HMG-14 and its mitogen-activated kinase with nuclease-sensitive mononucleosomes has implications for models of mitogen-stimulated IE gene induction.

MeSH Terms
Amino Acid Sequence Animals Anisomycin/pharmacology Cell Line Epidermal Growth Factor/pharmacology Genes, Immediate-Early/drug effects High Mobility Group Proteins/metabolism Mice Mice, Inbred C3H Micrococcal Nuclease Mitogens/pharmacology Molecular Sequence Data Nucleosomes/metabolism Phosphorylation Protein Kinases/drug effects,metabolism Protein Processing, Post-Translational Protein Synthesis Inhibitors/pharmacology Tetradecanoylphorbol Acetate/pharmacology
Chemicals
High Mobility Group Proteins Mitogens Nucleosomes Protein Synthesis Inhibitors Epidermal Growth Factor Anisomycin Protein Kinases Micrococcal Nuclease Tetradecanoylphorbol Acetate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Barratt M J
Nuclear Signalling Laboratory, Randall Institute, King's College London, UK.
Hazzalin C A
Zhelev N
Mahadevan L C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-10-03
Pages
4524-35
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395385
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source PMC Full Text View journal details
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