Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochemistry. 2008 Jun 24;47(25):6719-26. doi: 10.1021/bi800309m.

Biochemical analysis of MST1 kinase: elucidation of a C-terminal regulatory region.

Author information

1
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.

Abstract

The MST1 kinase phosphorylates FoxO transcription factors in the cytosol and histone H2B in the nucleus to promote cellular apoptosis. In addition to a N-terminal kinase domain, MST1 contains C-terminal regulatory and dimerization regions that are cleaved upon nuclear transport. In this report, we investigate the role of the MST1 regulatory region and dimerization domain in MST1 activity toward FoxO and histone H2B substrates. We find that the MST1 regulatory region enhances FoxO phosphorylation while inhibiting histone H2B phosphorylation, consistent with the cellular properties of MST1. We also identify autophosphorylation sites within the MST1 regulatory region and show that both regulatory region phosphorylation and MST1 dimerization contribute to FoxO phosphorylation. Together, our studies provide new insights into how MST1 substrate selectivity is modulated with implications for understanding apoptotic signaling through MST1 kinase.

PMID:
18510339
PMCID:
PMC2844906
DOI:
10.1021/bi800309m
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Support Center