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E-GEOD-37731 - The Akt-SRPK-SR axis constitutes a major pathway in transducing EGF signaling to regulate alternative splicing in the nucleus

Status
Released on 17 August 2012, last updated on 21 August 2013
Organism
Homo sapiens
Samples (12)
Protocols (14)
Description
Pre-mRNA splicing is regulated by developmental and environmental cues, but little is known about how specific signals are transduced in mammalian cells to regulate this critical gene expression step. Here, we report massive reprogramming of alternative splicing in response to EGF signaling. By blocking individual branches in EGF signaling, we found that Akt activation plays a major role, while other branches, such as the JAK/STAT and ERK pathways, make minor contributions to EGF-induced splicing. Activated Akt next branches to the SRPK family of kinases specific for SR proteins, rather than mTOR, by inducing SRPK autophosphorylation that switches the splicing kinases from Hsp70- to Hsp90-containing complexes. This leads to enhanced SRPK nuclear translocation and SR protein phosphorylation. These findings reveal a major signal transduction pathway for regulated splicing and place SRPKs in a central position in the pathway, consistent with their reputed roles in a large number of human cancers. Examination of EGF induced AKT-SRPK-SR pathway in the regulation of splicing in HEK293T cells with RASL-seq
Experiment type
other 
Contacts
Yu Zhou <geo@ncbi.nlm.nih.gov>, Gourisanker Ghosh, Hairi Li, Jinsong Qiu, Joseph A Adams, Michael G Rosenfeld, Qidong Hu, Ryan M Plocinik, Wen Liu, Xiang-Dong Fu, Zhihong Zhou
Citation
The Akt-SRPK-SR axis constitutes a major pathway in transducing EGF signaling to regulate alternative splicing in the nucleus. Zhou Z, Qiu J, Liu W, Zhou Y, Plocinik RM, Li H, Hu Q, Ghosh G, Adams JA, Rosenfeld MG, Fu XD. , PMID:22727668
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-37731.idf.txt
Sample and data relationshipE-GEOD-37731.sdrf.txt
Processed data (1)E-GEOD-37731.processed.1.zip
Links