iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://pubmed.ncbi.nlm.nih.gov/14583600
Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation - PubMed Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 Jan 9;279(2):1506-12.
doi: 10.1074/jbc.M308755200. Epub 2003 Oct 28.

Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation

Scott J Cameron  1 , Jun-Ichi Abe, Sundeep Malik, Wenyi Che, Jay Yang
Affiliations
Free article

Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation

Scott J Cameron et al. J Biol Chem. .
Free article

Abstract

Big mitogen-activated protein kinase 1/extracellular-regulated kinase 5 (BMK1/ERK5) is regulated sequentially by a series of upstream MAP kinase kinases (MEKs) in a signaling cascade. MEKs activate their downstream MAPK by phosphorylation of threonine and tyrosine in the T- X-Y motif. MEK5 is the upstream BMK1 kinase and exists as naturally occurring splice variants, MEK5alpha and MEK5beta. The full-length MEK5 (MEK5alpha) is 89 amino acids longer than MEK5beta at the N terminus, but the precise functional difference between the two splice variants is not known. Dual phosphorylation site mutation of MEK5alpha (Ser-311 --> Asp and Thr- 315 --> Asp; MEK5alpha(S311D/T315D)) activated BMK1, but the corresponding dual phosphorylation sites mutant of MEK5beta could not induce BMK1 kinase activation or nuclear translocation. Furthermore, MEK5beta inhibited epidermal growth factor-induced BMK1 activation and MEK5alpha(S311D/T315D)-induced MEF2 transcriptional activity. Both MEK5alpha and MEK5beta individually co-immunoprecipitated with BMK1, but the presence of MEK5beta prevented association of MEK5alpha with BMK1 suggesting a mechanistic basis for the dominant-negative behavior of MEK5beta on BMK1 activation. The ratio of MEK5alpha to MEK5beta expression was higher in cancer cell lines, and overexpression of MEK5beta-inhibited serum-induced DNA synthesis. These data suggest that alternative splicing of MEK5alpha and MEK5beta may play a critical role in BMK1 activation and subsequent cell proliferation.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources