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The Akt-SRPK-SR Axis Constitutes a Major Pathway in Transducing EGF Signaling to Regulate Alternative Splicing in the Nucleus
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Summary 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 SR protein-specific kinases, 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.
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Citations
Cites
Practical Nonparametric Statistics
Groggel, D. J. (2000) · Technometrics · doi:10.1080/00401706.2000.10486067 · Cited by 11,041
Expansion of the eukaryotic proteome by alternative splicing
Nilsen, T. W., & Graveley, B. R. (2010) · Nature · doi:10.1038/nature08909 · Cited by 2,197
Epidermal growth factor receptor: Mechanisms of activation and signalling
Jorissen, R. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00098-8 · Cited by 1,565
Practical Nonparametric Statistics
Bhapkar, V., & Conover, W. J. (1972) · Technometrics · doi:10.2307/1267149 · Cited by 1,410
Cooper, T. A., Wan, L., & Dreyfuss, G. (2009) · Cell · doi:10.1016/j.cell.2009.02.011 · Cited by 1,159
An extensive network of coupling among gene expression machines
Maniatis, T., & Reed, R. (2002) · Nature · doi:10.1038/416499a · Cited by 1,146
Dysregulation of the TSC-mTOR pathway in human disease
Inoki, K., Corradetti, M. N., & Guan, K.-L. (2005) · Nature Genetics · doi:10.1038/ng1494 · Cited by 972
The PTEN–PI3K pathway: of feedbacks and cross-talks
Carracedo, A., & Pandolfi, P. P. (2008) · Oncogene · doi:10.1038/onc.2008.247 · Cited by 878
Hirai, H., Sootome, H., Nakatsuru, Y., Miyama, K., Taguchi, S., Tsujioka, K., Ueno, Y., Hatch, H., Majumder, P. K., Pan, B.-S., et al. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-1012 · Cited by 860
Pre-mRNA Processing Reaches Back toTranscription and Ahead to Translation
Moore, M. J., & Proudfoot, N. J. (2009) · Cell · doi:10.1016/j.cell.2009.02.001 · Cited by 846
McCormack, A. L., Schieltz, D. M., Goode, B., Yang, S., Barnes, G., Drubin, D., & Yates, J. R. (1997) · Analytical Chemistry · doi:10.1021/ac960799q · Cited by 523
Dynamic Protein-Protein Interaction Wiring of the Human Spliceosome
Hegele, A., Kamburov, A., Grossmann, A., Sourlis, C., Wowro, S., Weimann, M., Will, C. L., Pena, V., Lührmann, R., & Stelzl, U. (2012) · Molecular Cell · doi:10.1016/j.molcel.2011.12.034 · Cited by 414
Du, H., Cline, M. S., Osborne, R. J., Tuttle, D. L., Clark, T. A., Donohue, J. P., Hall, M. P., Shiue, L., Swanson, M. S., Thornton, C. A., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1720 · Cited by 332
Wang, H.-Y., Lin, W., Dyck, J. A., Yeakley, J. M., Songyang, Z., Cantley, L. C., & Fu, X.-D. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.4.737 · Cited by 324
Self-citationSong, J., Takeda, M., & Morimoto, R. I. (2001) · Nature Cell Biology · doi:10.1038/35060068 · Cited by 284
Cell signalling and the control of pre-mRNA splicing
Shin, C., & Manley, J. L. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1467 · Cited by 273
WT1 Mutants Reveal SRPK1 to Be a Downstream Angiogenesis Target by Altering VEGF Splicing
Amin, E. M., Oltean, S., Hua, J., Gammons, M. V. R., Hamdollah-Zadeh, M., Welsh, G. I., Cheung, M.-K., Ni, L., Kase, S., Rennel, E. S., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.10.016 · Cited by 253
Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT
Blaustein, M., Pelisch, F., Tanos, T., Muñoz, M. J., Wengier, D., Quadrana, L., Sanford, J. R., Muschietti, J. P., Kornblihtt, A. R., Cáceres, J. F., et al. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1020 · Cited by 246
Cho, S., Hoang, A., Sinha, R., Zhong, X.-Y., Fu, X.-D., Krainer, A. R., & Ghosh, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017700108 · Cited by 235
Self-citationZhong, X.-Y., Ding, J.-H., Adams, J. A., Ghosh, G., & Fu, X.-D. (2009) · Genes & Development · doi:10.1101/gad.1752109 · Cited by 229
Self-citationSR Proteins and Related Factors in Alternative Splicing
Lin, S., & Fu, X.-D. (2007) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-387-77374-2_7 · Cited by 214
Self-citationProfiling alternative splicing on fiber-optic arrays
Yeakley, J. M., Fan, J.-B., Doucet, D., Luo, L., Wickham, E., Ye, Z., Chee, M. S., & Fu, X.-D. (2002) · Nature Biotechnology · doi:10.1038/nbt0402-353 · Cited by 207
Self-citationNgo, J. C. K., Chakrabarti, S., Ding, J.-H., Velazquez-Dones, A., Nolen, B., Aubol, B. E., Adams, J. A., Fu, X.-D., & Ghosh, G. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.025 · Cited by 206
Self-citationNEW EMBO MEMBERS' REVIEW: Hsp70 interactions with the p53 tumour suppressor protein
Zylicz, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.17.4634 · Cited by 192
Yang, X., Bani, M. R., Lu, S. J., Rowan, S., Ben-David, Y., & Chabot, B. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.15.6924 · Cited by 191
Regulation of alternative pre-mRNA splicing by the ERK MAP-kinase pathway
Weg-Remers, S. (2001) · The EMBO Journal · doi:10.1093/emboj/20.15.4194 · Cited by 184
Functional integration of transcriptional and RNA processing machineries
Pandit, S., Wang, D., & Fu, X.-D. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.03.001 · Cited by 173
Self-citationHayes, G. M., Carrigan, P. E., & Miller, L. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2969 · Cited by 171
King, F. W. (2001) · The EMBO Journal · doi:10.1093/emboj/20.22.6297 · Cited by 167
Coupling of signal transduction to alternative pre-mRNA splicing by a composite splice regulator
Konig, H. (1998) · The EMBO Journal · doi:10.1093/emboj/17.10.2904 · Cited by 159
Mathew, R. S., Hartmuth, K., Möhlmann, S., Urlaub, H., Ficner, R., & Lührmann, R. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1415 · Cited by 145
Lynch, K. W., & Weiss, A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.1.70-80.2000 · Cited by 144
Hernández, F., Pérez, M., Lucas, J. J., Mata, A. M., Bhat, R. V., & Ávila, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311512200 · Cited by 140
Conservation in budding yeast of a kinase specific for SR splicing factors
Siebel, C. W., Feng, L. L., Guthrie, C., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5440 · Cited by 138
Regulated Cellular Partitioning of SR Protein-specific Kinases in Mammalian Cells
Ding, J., Zhong, X.-Y., Hagopian, J. C., Cruz, M. M., Ghosh, G., Feramisco, J. R., Adams, J. A., & Fu, X. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-10-0963 · Cited by 132
Self-citationShultz, J. C., Goehe, R. W., Wijesinghe, D. S., Murudkar, C. S., Hawkins, A. J., Shay, J. W., Minna, J. D., & Chalfant, C. E. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1545 · Cited by 132
Interaction of Akt-phosphorylated SRPK2 with 14-3-3 Mediates Cell Cycle and Cell Death in Neurons
Jang, S., Liu, X., Fu, H., Rees, H. D., Yepes, M., Levey, A. I., & Ye, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.026237 · Cited by 131
Phosphorylation-Dependent Regulation of PSF by GSK3 Controls CD45 Alternative Splicing
Heyd, F., & Lynch, K. W. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.013 · Cited by 128
Shi, Y., & Manley, J. L. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.08.028 · Cited by 123
Targeting the RNA Splicing Machinery as a Novel Treatment Strategy for Pancreatic Carcinoma
Hayes, G. M., Carrigan, P. E., Beck, A. M., & Miller, L. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4065 · Cited by 121
Processive phosphorylation of alternative splicing factor/splicing factor 2
Aubol, B. E., Chakrabarti, S., Ngo, J. C. K., Shaffer, J., Nolen, B. J., Fu, X., Ghosh, G., & Adams, J. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1635129100 · Cited by 117
Self-citationRASL‐seq for Massively Parallel and Quantitative Analysis of Gene Expression
Li, H., Qiu, J., & Fu, X. (2012) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb0413s98 · Cited by 106
Self-citationRegulation of Alternative Splicing by Signal Transduction Pathways
Lynch, K. W. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-77374-2_10 · Cited by 87
Jiang, K., Patel, N. A., Watson, J. E., Apostolatos, H. S., Kleiman, E., Hanson, O., Hagiwara, M., & Cooper, D. R. (2008) · Endocrinology · doi:10.1210/en.2008-0818 · Cited by 86
DEGRADE, MOVE, REGROUP: signaling control of splicing proteins
Heyd, F., & Lynch, K. W. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.04.003 · Cited by 82
The structure of Sky1p reveals a novel mechanism for constitutive activity.
Nolen, B. J., Yun, C. Y., Wong, C. F., McCammon, J. A., Fu, X., & Ghosh, G. (2001) · Nature Structural Biology · doi:10.1038/84178 · Cited by 76
Self-citationPlasencia, C., Martinez‐Balibrea, E., Martínez‐Cardús, A., Quinn, D. I., Abad, A., & Neamati, N. (2006) · International Journal of Oncology · doi:10.3892/ijo.29.1.225 · Cited by 69
Kinome siRNA-phosphoproteomic screen identifies networks regulating AKT signaling
Lu, Y., Müller, M. M., Smith, D. M., Dutta, B., Komurov, K., Iadevaia, S., Ruths, D. A., Tseng, J.-T., Yu, S., Yu, Q., et al. (2011) · Oncogene · doi:10.1038/onc.2011.164 · Cited by 68
SRPK1: A cisplatin sensitive protein expressed in retinoblastoma
Krishnakumar, S., Mohan, A., Kandalam, M., Ramkumar, H. L., Venkatesan, N., & Das, R. R. (2006) · Pediatric Blood & Cancer · doi:10.1002/pbc.21088 · Cited by 46
Liu, X., Mayeda, A., Tao, M., & Zheng, Z. (2003) · Journal of Virology · doi:10.1128/jvi.77.3.2105-2115.2003 · Cited by 43
Zhang, X., Clark, A. F., & Yorio, T. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-0697 · Cited by 38
Serological identification of adult T‐cell leukaemia‐associated antigens
Hishizawa, M., Imada, K., Sakai, T., Ueda, M., Hori, T., & Uchiyama, T. (2005) · British Journal of Haematology · doi:10.1111/j.1365-2141.2005.05619.x · Cited by 26
Cited by
Context-dependent control of alternative splicing by RNA-binding proteins
Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044
Self-citationAlternative splicing: a pivotal step between eukaryotic transcription and translation
Kornblihtt, A. R., Schor, I. E., Alló, M., Dujardin, G., Petrillo, E., & Muñoz, M. J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3525 · Cited by 853
Hallmarks of alternative splicing in cancer
Oltean, S., & Bates, D. O. (2014) · Oncogene · doi:10.1038/onc.2013.533 · Cited by 664
Urbanski, L. M., Leclair, N., & Anczuków, O. (2018) · WIREs RNA · doi:10.1002/wrna.1476 · Cited by 389
Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate
Fong, N., Kim, H., Zhou, Y., Ji, X., Qiu, J., Saldi, T., Diener, K., Jones, K., Fu, X.-D., & Bentley, D. L. (2014) · Genes & Development · doi:10.1101/gad.252106.114 · Cited by 287
Self-citation
Metadata
- Authors
- Zhou, Z., Qiu, J., Liu, W., Zhou, Y., Plocinik, R. M., Li, H., Hu, Q., Ghosh, G., Adams, J. A., Rosenfeld, M. G., & Fu, X.-D.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 47
- Issue
- 3
- Pages
- 422-433
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1986818022
- Cited by
- 273
- References
- 52
- FWCI
- 8.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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