Journal article
Mitogen-Activated Protein Kinase Phosphorylation of Splicing Factor 45 (SPF45) Regulates SPF45 Alternative Splicing Site Utilization, Proliferation, and Cell Adhesion
Molecular and cellular biology, Vol.32(14), pp.2880-2893
07/01/2012
DOI: 10.1128/MCB.06327-11
PMCID: PMC3416182
PMID: 22615491
Abstract
The regulation of alternative mRNA splicing factors by extracellular cues and signal transduction cascades is poorly understood. Using an engineered extracellular signal-regulated kinase 2 (ERK2) that can utilize ATP analogs, we have identified the alternative mRNA splicing factor 45 (SPF45), which is overexpressed in cancer, as a novel coimmunoprecipitating ERK2 substrate. ERK2 phosphorylated SPF45 on Thr71 and Ser222 in vitro and in cells in response to H-RasV12, B-RAF-V600E, and activated MEK1. Jun N-terminal kinase 1 (JNK1) and p38 alpha also phosphorylated SPF45 in vitro and associated with SPF45 in cells. SPF45 was differentially phosphorylated in cells by all three mitogen-activated protein (MAP) kinases in response to phorbol myristate acid (PMA), H2O2, UV, and anisomycin stimulation. ERK and p38 activation decreased SPF45-dependent exon 6 exclusion from fas mRNA in a minigene assay in cells. Stable overexpression of SPF45 in SKOV-3 cells dramatically inhibited cell proliferation in a phosphorylation-dependent manner through inhibition of ErbB2 expression. SPF45 overexpression also induced EDA inclusion into fibronectin transcripts and fibronectin expression in a phosphorylation-dependent and -independent manner, respectively, specifically affecting cellular adhesion to a fibronectin matrix. These data identify SPF45 as the first splicing factor regulated by multiple MAP kinase pathways and show effects of both SPF45 overexpression and phosphorylation.
Details
- Title: Subtitle
- Mitogen-Activated Protein Kinase Phosphorylation of Splicing Factor 45 (SPF45) Regulates SPF45 Alternative Splicing Site Utilization, Proliferation, and Cell Adhesion
- Creators
- Adnan M. Al-Ayoubi - Med Univ S Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USAHui Zheng - Medical University of South CarolinaYuying Liu - Medical University of South CarolinaTao Bai - Medical University of South CarolinaScott T. Eblen - Medical University of South Carolina
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.32(14), pp.2880-2893
- DOI
- 10.1128/MCB.06327-11
- PMID
- 22615491
- PMCID
- PMC3416182
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Publisher
- Amer Soc Microbiology
- Number of pages
- 14
- Grant note
- 1R01CA131200 / National Cancer Institute/National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA131200 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) W81XWH-07-1-0691 / Department of Defense; United States Department of Defense
- Language
- English
- Date published
- 07/01/2012
- Academic Unit
- Cardiothoracic Surgery
- Record Identifier
- 9984701728702771
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