Hình ảnh cấu trúc của các tương tác kinase RAF
Tóm tắt
RAF (fibrosarcoma gia tốc nhanh) Ser/Thr kinases (ARAF, BRAF, và CRAF) liên kết gia đình protein RAS (rat sarcoma) với con đường MAPK (kinase protein được kích hoạt bởi tác nhân gây tăng trưởng) và điều khiển sự tăng trưởng tế bào, phân hóa, phát triển, lão hóa và sinh ung thư. Hoạt động của chúng được điều chỉnh đặc biệt thông qua các tương tác protein-protein, các sửa đổi sau dịch mã, và sự thay đổi cấu hình trong các mẫu thời gian và không gian cụ thể qua nhiều điều tiết upstream, bao gồm các kinase, phosphatase, GTPases, và các protein khung và điều chỉnh. Việc khử phosphoryl hóa Ser-259 (theo số CRAF) và sự tách ra của 14-3-3 giải phóng các miền điều chỉnh của RAF, miền liên kết RAS và miền giàu cysteine, để tương tác với RAS-GTP và các lipid màng. Điều này dẫn đến việc phosphoryl hóa RAF tại Ser-621 và sự tái kết hợp 14-3-3, tiếp theo là sự dimer hóa của nó và cuối cùng là sự liên kết và phosphoryl hóa cơ chất. Bài tổng quan này tập trung vào việc hiểu cấu trúc cách mà các đối tác liên kết khác nhau kích hoạt một chuỗi sự kiện phân tử dẫn đến việc kích hoạt kinase RAF.
Từ khóa
Tài liệu tham khảo
Rapp, 1983, Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus, Proc. Natl Acad. Sci. U.S.A., 80, 4218, 10.1073/pnas.80.14.4218
Bonner, 1985, Structure and biological activity of human homologs of the raf/mil oncogene, Mol. Cell. Biol., 5, 1400, 10.1128/MCB.5.6.1400
Huleihel, 1986, Characterization of murine A-raf, a new oncogene related to the v-raf oncogene, Mol. Cell. Biol., 6, 2655, 10.1128/MCB.6.7.2655
Ikawa, 1988, B-raf, a new member of the raf family, is activated by DNA rearrangement, Mol. Cell. Biol., 8, 2651, 10.1128/MCB.8.6.2651
Han, 1993, C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation, Nature, 363, 133, 10.1038/363133a0
Mark, 1987, Drosophila melanogaster homologs of the raf oncogene, Mol. Cell. Biol., 7, 2134, 10.1128/MCB.7.6.2134
Hsu, 2002, Caenorhabditis elegans lin-45 raf is essential for larval viability, fertility and the induction of vulval cell fates, Genetics, 160, 481, 10.1093/genetics/160.2.481
Morrison, 1990, The Raf-1 kinase as a transducer of mitogenic signals, Cancer Cells, 2, 377
Avruch, 2001, Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade, Recent Prog. Horm. Res., 56, 127, 10.1210/rp.56.1.127
Wellbrock, 2004, The RAF proteins take centre stage, Nat. Rev. Mol. Cell Biol., 5, 875, 10.1038/nrm1498
Leicht, 2007, Raf kinases: function, regulation and role in human cancer, Biochim. Biophys. Acta, 1773, 1196, 10.1016/j.bbamcr.2007.05.001
Osborne, 2012, Signal control through Raf: in sickness and in health, Cell Res., 22, 14, 10.1038/cr.2011.193
Desideri, 2015, Alike but different: RAF paralogs and their signaling outputs, Cell, 161, 967, 10.1016/j.cell.2015.04.045
Sanges, 2012, Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells, Cell Death Dis., 3, e276, 10.1038/cddis.2012.16
An, 2015, A-Raf: a new star of the family of raf kinases, Crit. Rev. Biochem. Mol. Biol., 50, 520, 10.3109/10409238.2015.1102858
Downward, 2003, Targeting RAS signalling pathways in cancer therapy, Nat. Rev. Cancer, 3, 11, 10.1038/nrc969
Maurer, 2011, Raf kinases in cancer-roles and therapeutic opportunities, Oncogene, 30, 3477, 10.1038/onc.2011.160
Roring, 2012, Aberrant B-Raf signaling in human cancer — 10 years from bench to bedside, Crit. Rev. Oncog., 17, 97, 10.1615/CritRevOncog.v17.i1.70
Allanson, 2011, Cardio-facio-cutaneous syndrome: does genotype predict phenotype?, Am. J. Med. Genet. C Semin. Med. Genet., 157, 129, 10.1002/ajmg.c.30295
Tartaglia, 2011, Noonan syndrome and clinically related disorders, Best Pract. Res. Clin. Endocrinol. Metab., 25, 161, 10.1016/j.beem.2010.09.002
Vandamme, 2014, Regulation of the MAPK pathway by raf kinase inhibitory protein, Crit. Rev. Oncogenesis, 19, 405, 10.1615/CritRevOncog.2014011922
Morrison, 1997, The complexity of Raf-1 regulation, Curr. Opin. Cell Biol., 9, 174, 10.1016/S0955-0674(97)80060-9
Roberts, 2007, Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer, Oncogene, 26, 3291, 10.1038/sj.onc.1210422
Karnoub, 2008, Ras oncogenes: split personalities, Nat. Rev. Mol. Cell Biol., 9, 517, 10.1038/nrm2438
Rauch, 2016, MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance, Curr. Opin. Struct. Biol., 41, 151, 10.1016/j.sbi.2016.07.019
Zhang, 1993, Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1, Nature, 364, 308, 10.1038/364308a0
Vojtek, 1993, Mammalian Ras interacts directly with the serine/threonine kinase Raf, Cell, 74, 205, 10.1016/0092-8674(93)90307-C
Moodie, 1993, Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase, Science, 260, 1658, 10.1126/science.8503013
Warne, 1993, Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro, Nature, 364, 352, 10.1038/364352a0
Van Aelst, 1993, Complex formation between RAS and RAF and other protein kinases, Proc. Natl Acad. Sci. U.S.A., 90, 6213, 10.1073/pnas.90.13.6213
Matallanas, 2011, Raf family kinases: old dogs have learned new tricks, Genes Cancer, 2, 232, 10.1177/1947601911407323
Baljuls, 2013, It takes two to tango — signalling by dimeric Raf kinases, Mol. Biosyst., 9, 551, 10.1039/C2MB25393C
Marais, 1997, Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine kinases, J. Biol. Chem., 272, 4378, 10.1074/jbc.272.7.4378
Leicht, 2013, MEK-1 activates C-Raf through a Ras-independent mechanism, Biochim. Biophys. Acta, 1833, 976, 10.1016/j.bbamcr.2013.01.015
Rushworth, 2006, Regulation and role of Raf-1/B-Raf heterodimerization, Mol. Cell. Biol., 26, 2262, 10.1128/MCB.26.6.2262-2272.2006
Rodriguez-Viciana, 2006, A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity, Mol. Cell, 22, 217, 10.1016/j.molcel.2006.03.027
Freeman, 2013, The importance of Raf dimerization in cell signaling, Small GTPases, 4, 180, 10.4161/sgtp.26117
Lavoie, 2014, Dimerization-induced allostery in protein kinase regulation, Trends Biochem. Sci., 39, 475, 10.1016/j.tibs.2014.08.004
Lavoie, 2015, Regulation of RAF protein kinases in ERK signalling, Nat. Rev. Mol. Cell Biol., 16, 281, 10.1038/nrm3979
Gutierrez-Erlandsson, 2013, R-RAS2 overexpression in tumors of the human central nervous system, Mol. Cancer, 12, 127, 10.1186/1476-4598-12-127
Herrmann, 2003, Ras-effector interactions: after one decade, Curr. Opin. Struct. Biol., 13, 122, 10.1016/S0959-440X(02)00007-6
Castellano, 2010, Role of RAS in the regulation of PI 3-kinase, Curr. Top. Microbiol. Immunol., 346, 143
Rajalingam, 2007, Ras oncogenes and their downstream targets, Biochim. Biophys. Acta, 1773, 1177, 10.1016/j.bbamcr.2007.01.012
Nakhaei-Rad, 2018, Structural fingerprints, interactions, and signaling networks of RAS family proteins beyond RAS isoforms, Crit. Rev. Biochem. Mol. Biol., 53, 130, 10.1080/10409238.2018.1431605
Repasky, 2004, Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis?, Trends Cell Biol., 14, 639, 10.1016/j.tcb.2004.09.014
Wohlgemuth, 2005, Recognizing and defining true Ras binding domains I: biochemical analysis, J. Mol. Biol., 348, 741, 10.1016/j.jmb.2005.02.048
Nakhaeizadeh, 2016, The RAS-effector interface: isoform-specific differences in the effector binding regions, PLoS ONE, 11, e0167145, 10.1371/journal.pone.0167145
Patel, 2013, Ras GTPases’ interaction with effector domains: breaking the families’ barrier, Commun. Integr. Biol., 6, e24298, 10.4161/cib.24298
Herrmann, 1996, Ras and its effectors, Prog. Biophys. Mol. Biol., 66, 1, 10.1016/S0079-6107(96)00015-6
Mott, 2015, Structures of Ras superfamily effector complexes: what have we learnt in two decades?, Crit. Rev. Biochem. Mol. Biol., 50, 85, 10.3109/10409238.2014.999191
Mazhab-Jafari, 2015, Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site, Proc. Natl Acad. Sci. U.S.A., 112, 6625, 10.1073/pnas.1419895112
Vetter, 2001, The guanine nucleotide-binding switch in three dimensions, Science, 294, 1299, 10.1126/science.1062023
Drugan, 1996, Ras interaction with two distinct binding domains in Raf-1 5 be required for Ras transformation, J. Biol. Chem., 271, 233, 10.1074/jbc.271.1.233
Thapar, 2004, NMR characterization of full-length farnesylated and non-farnesylated H-Ras and its implications for Raf activation, J. Mol. Biol., 343, 1391, 10.1016/j.jmb.2004.08.106
Athuluri-Divakar, 2016, A small molecule RAS-mimetic disrupts RAS association with effector proteins to block signaling, Cell, 165, 643, 10.1016/j.cell.2016.03.045
Nassar, 1995, The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue, Nature, 375, 554, 10.1038/375554a0
Huang, 1998, Structural basis for the interaction of Ras with RalGDS, Nat. Struct. Biol., 5, 422, 10.1038/nsb0698-422
Stieglitz, 2008, Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II, EMBO J., 27, 1995, 10.1038/emboj.2008.125
Pacold, 2000, Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma, Cell, 103, 931, 10.1016/S0092-8674(00)00196-3
Bunney, 2006, Structural and mechanistic insights into ras association domains of phospholipase C epsilon, Mol. Cell, 21, 495, 10.1016/j.molcel.2006.01.008
Marshall, 1993, The effector interactions of p21ras, Trends Biochem. Sci., 18, 250, 10.1016/0968-0004(93)90175-M
Wittinghofer, 1995, Ras-effector interactions, the problem of specificity, FEBS Lett., 369, 52, 10.1016/0014-5793(95)00667-X
Wittinghofer, 1996, How Ras-related proteins talk to their effectors, Trends Biochem. Sci., 21, 488, 10.1016/S0968-0004(96)10064-5
Wittinghofer, 1998, Signal transduction via Ras, Biol. Chem., 379, 933
Corbett, 2001, The many faces of Ras: recognition of small GTP-binding proteins, Trends Biochem. Sci., 26, 710, 10.1016/S0968-0004(01)01974-0
Spaargaren, 1994, The Ras-related protein R-ras interacts directly with Raf-1 in a GTP-dependent manner, Biochem. J., 300, 303, 10.1042/bj3000303
Koide, 1993, GTP-dependent association of Raf-1 with Ha-Ras: identification of Raf as a target downstream of Ras in mammalian cells, Proc. Natl Acad. Sci. U.S.A., 90, 8683, 10.1073/pnas.90.18.8683
Barnard, 1995, Identification of the sites of interaction between c-Raf-1 and Ras-GTP, Oncogene, 10, 1283
Herrmann, 1995, Quantitative analysis of the complex between p21 and the ras-binding domain of the human raf-1 protein kinase, J. Biol. Chem., 270, 2901, 10.1074/jbc.270.7.2901
Nassar, 1996, Ras/Rap effector specificity determined by charge reversal, Nat. Struct. Biol., 3, 723, 10.1038/nsb0896-723
Lavoie, 2018, MEK drives BRAF activation through allosteric control of KSR proteins, Nature, 554, 549, 10.1038/nature25478
Filchtinski, 2010, What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf, J Mol Biol., 399, 422, 10.1016/j.jmb.2010.03.046
Fetics, 2015, Allosteric effects of the oncogenic RasQ61L mutant on Raf-RBD, Structure, 23, 505, 10.1016/j.str.2014.12.017
Mott, 1996, The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site, Proc. Natl Acad. Sci., 93, 8312, 10.1073/pnas.93.16.8312
Molzan, 2010, Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in diseases with increased Ras signaling, Mol. Cell. Biol., 30, 4698, 10.1128/MCB.01636-09
Molzan, 2012, Synergistic binding of the phosphorylated S233-and S259-binding sites of C-RAF to one 14-3-3ζ dimer, J. Mol. Biol., 423, 486, 10.1016/j.jmb.2012.08.009
Molzan, 2013, Stabilization of physical RAF/14-3-3 interaction by cotylenin A as treatment strategy for RAS mutant cancers, ACS Chem. Biol., 8, 1869, 10.1021/cb4003464
Wan, 2004, Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF, Cell, 116, 855, 10.1016/S0092-8674(04)00215-6
Haling, 2014, Structure of the BRAF-MEK complex reveals a kinase activity independent role for BRAF in MAPK signaling, Cancer Cell, 26, 402, 10.1016/j.ccr.2014.07.007
Sprang, 1995, How Ras works: structure of a Rap-Raf complex, Structure, 3, 641, 10.1016/S0969-2126(01)00198-8
Erijman, 2016, RAS/effector interactions from structural and biophysical perspective, Mini-Rev. Med. Chem., 16, 370, 10.2174/1389557515666151001141838
Block, 1996, Quantitative structure-activity analysis correlating Ras/Raf interaction in vitro to Raf activation in vivo, Nat. Struct. Biol., 3, 244, 10.1038/nsb0396-244
Fridman, 2000, Point mutants of c-raf-1 RBD with elevated binding to v-Ha-Ras, J. Biol. Chem., 275, 30363, 10.1074/jbc.M003193200
Zehir, 2017, Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients, Nat. Med., 23, 703, 10.1038/nm.4333
Zeng, 1999, Protein-protein recognition: an experimental and computational study of the R89K mutation in Raf and its effect on Ras binding, Protein Sci., 8, 50, 10.1110/ps.8.1.50
Weber, 2000, Mitogenic signaling of Ras is regulated by differential interaction with Raf isozymes, Oncogene, 19, 169, 10.1038/sj.onc.1203261
Lim, 2015, Genome-wide mutation profiles of colorectal tumors and associated liver metastases at the exome and transcriptome levels, Oncotarget, 6, 22179, 10.18632/oncotarget.4246
Lefebvre, 2016, Mutational profile of metastatic breast cancers: a retrospective analysis, PLoS Med., 13, e1002201, 10.1371/journal.pmed.1002201
Terada, 1999, Nuclear magnetic resonance and molecular dynamics studies on the interactions of the Ras-binding domain of Raf-1 with wild-type and mutant Ras proteins, J. Mol. Biol., 286, 219, 10.1006/jmbi.1998.2472
Kiel, 2009, Improved binding of raf to Ras.GDP is correlated with biological activity, J. Biol. Chem., 284, 31893, 10.1074/jbc.M109.031153
Chavan, 2015, Plasma membrane regulates Ras signaling networks, Cell Logist., 5, e1136374, 10.1080/21592799.2015.1136374
Bondeva, 2002, Structural determinants of Ras-Raf interaction analyzed in live cells, Mol. Biol. Cell., 13, 2323, 10.1091/mbc.e02-01-0019
Nekhoroshkova, 2009, A-RAF kinase functions in ARF6 regulated endocytic membrane traffic, PLoS ONE, 4, e4647, 10.1371/journal.pone.0004647
Giannakis, 2016, Genomic correlates of immune-cell infiltrates in colorectal carcinoma, Cell Rep., 15, 857, 10.1016/j.celrep.2016.03.075
George, 2015, Comprehensive genomic profiles of small cell lung cancer, Nature, 524, 47, 10.1038/nature14664
Mouradov, 2014, Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer, Cancer Res., 74, 3238, 10.1158/0008-5472.CAN-14-0013
Fischer, 2007, B- and C-RAF display essential differences in their binding to Ras: the isotype-specific N terminus of B-RAF facilitates Ras binding, J. Biol. Chem., 282, 26503, 10.1074/jbc.M607458200
Chuang, 1994, Critical binding and regulatory interactions between Ras and Raf occur through a small, stable N-terminal domain of Raf and specific Ras effector residues, Mol. Cell. Biol., 14, 5318, 10.1128/MCB.14.8.5318
Li, 2018, A ‘Tug of War’ maintains a dynamic protein-membrane complex: molecular dynamics simulations of C-Raf RBD-CRD bound to K-Ras4B at an anionic membrane, ACS Cent. Sci., 4, 298, 10.1021/acscentsci.7b00593
Abaan, 2013, The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology, Cancer Res., 73, 4372, 10.1158/0008-5472.CAN-12-3342
Li, 2018, Raf-1 cysteine-Rich domain increases the affinity of K-Ras/Raf at the membrane, promoting MAPK signaling, Structure, 26, 513, 10.1016/j.str.2018.01.011
Brtva, 1995, Two distinct Raf domains mediate interaction with Ras, J. Biol. Chem., 270, 9809, 10.1074/jbc.270.17.9809
Hu, 1995, Cysteine-rich region of Raf-1 interacts with activator domain of post-translationally modified Ha-Ras, J. Biol. Chem., 270, 30274, 10.1074/jbc.270.51.30274
Hu, 1997, Coassociation of Rap1A and Ha-Ras with Raf-1 N-terminal region interferes with ras-dependent activation of Raf-1, J. Biol. Chem., 272, 11702, 10.1074/jbc.272.18.11702
Roy, 1997, Activity of plasma membrane-recruited Raf-1 is regulated by Ras via the Raf zinc finger, J. Biol. Chem., 272, 20139, 10.1074/jbc.272.32.20139
Luo, 1997, An intact Raf zinc finger is required for optimal binding to processed Ras and for ras-dependent Raf activation in situ, Mol. Cell. Biol., 17, 46, 10.1128/MCB.17.1.46
Daub, 1998, The RafC1 cysteine-rich domain contains multiple distinct regulatory epitopes which control Ras-dependent Raf activation, Mol. Cell. Biol., 18, 6698, 10.1128/MCB.18.11.6698
Okada, 1999, The strength of interaction at the Raf cysteine-rich domain is a critical determinant of response of Raf to Ras family small GTPases, Mol. Cell. Biol., 19, 6057, 10.1128/MCB.19.9.6057
Williams, 2000, Elucidation of binding determinants and functional consequences of Ras/Raf-cysteine-rich domain interactions, J. Biol. Chem., 275, 22172, 10.1074/jbc.M000397200
Chan, 2002, Mutations in conserved regions 1, 2, and 3 of Raf-1 that activate transforming activity, Mol. Carcinog., 33, 189, 10.1002/mc.10031
Hibino, 2011, Activation kinetics of RAF protein in the ternary complex of RAF, RAS-GTP, and kinase on the plasma membrane of living cells: single-molecule imaging analysis, J. Biol. Chem., 286, 36460, 10.1074/jbc.M111.262675
Ke, 2017, Structural basis for intramolecular interaction of post-translationally modified H-Ras*GTP prepared by protein ligation, FEBS Lett., 591, 2470, 10.1002/1873-3468.12759
Ghosh, 1994, The cysteine-rich region of raf-1 kinase contains zinc, translocates to liposomes, and is adjacent to a segment that binds GTP-ras, J. Biol. Chem., 269, 10000, 10.1016/S0021-9258(17)36981-8
Hekman, 2002, Associations of B- and C-Raf with cholesterol, phosphatidylserine, and lipid second messengers: preferential binding of Raf to artificial lipid rafts, J. Biol. Chem., 277, 24090, 10.1074/jbc.M200576200
Ghosh, 1996, Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-O-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells, J. Biol. Chem., 271, 8472, 10.1074/jbc.271.14.8472
Zang, 2001, Microtubule integrity regulates Pak leading to Ras-independent activation of Raf-1. Insights into mechanisms of Raf-1 activation, J. Biol. Chem., 276, 25157, 10.1074/jbc.M100152200
Improta-Brears, 1999, Mutational analysis of Raf-1 cysteine rich domain: requirement for a cluster of basic aminoacids for interaction with phosphatidylserine, Mol. Cell. Biochem., 198, 171, 10.1023/A:1006981411691
Sarkozy, 2009, Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum, Hum. Mutat., 30, 695, 10.1002/humu.20955
Abankwa, 2007, Ras nanoclusters: molecular structure and assembly, Semin. Cell Dev. Biol., 18, 599, 10.1016/j.semcdb.2007.08.003
Abankwa, 2010, Ras membrane orientation and nanodomain localization generate isoform diversity, Proc. Natl Acad. Sci. U.S.A., 107, 1130, 10.1073/pnas.0903907107
Cirstea, 2010, A restricted spectrum of NRAS mutations causes Noonan syndrome, Nat. Genet., 42, 27, 10.1038/ng.497
Kapoor, 2012, Revealing conformational substates of lipidated N-Ras protein by pressure modulation, Proc. Natl Acad. Sci. U.S.A., 109, 460, 10.1073/pnas.1110553109
Vogel, 2014, Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity, Biol. Chem., 395, 779, 10.1515/hsz-2013-0294
Sperlich, 2016, Regulation of K-Ras4B membrane binding by calmodulin, Biophys. J., 111, 113, 10.1016/j.bpj.2016.05.042
Erwin, 2017, Influence of isoform-specific Ras lipidation motifs on protein partitioning and dynamics in model membrane systems of various complexity, Biol. Chem., 398, 290, 10.1515/hsz-2016-0289
Dumaz, 2003, Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras, J. Biol. Chem., 278, 29819, 10.1074/jbc.C300182200
Sendoh, 2000, Role of Raf-1 conserved region 2 in regulation of Ras-dependent Raf-1 activation, Biochem. Biophys. Res. Commun., 271, 596, 10.1006/bbrc.2000.2674
Dhillon, 2002, Regulation of Raf-1 activation and signalling by dephosphorylation, EMBO J., 21, 64, 10.1093/emboj/21.1.64
Dhillon, 2002, Cyclic AMP-dependent kinase regulates Raf-1 kinase mainly by phosphorylation of serine 259, Mol. Cell. Biol., 22, 3237, 10.1128/MCB.22.10.3237-3246.2002
Zimmermann, 1999, Phosphorylation and regulation of Raf by Akt (protein kinase B), Science, 286, 1741, 10.1126/science.286.5445.1741
Rommel, 1999, Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt, Science, 286, 1738, 10.1126/science.286.5445.1738
Pandit, 2007, Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy, Nat. Genet., 39, 1007, 10.1038/ng2073
Razzaque, 2007, Germline gain-of-function mutations in RAF1 cause Noonan syndrome, Nat. Genet., 39, 1013, 10.1038/ng2078
Kobayashi, 2010, Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation, Hum. Mutat., 31, 284, 10.1002/humu.21187
Hodis, 2012, A landscape of driver mutations in melanoma, Cell, 150, 251, 10.1016/j.cell.2012.06.024
Martin, 2014, The head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies, Oncotarget, 5, 8906, 10.18632/oncotarget.2417
Shi, 2016, Somatic genomics and clinical features of lung adenocarcinoma: a retrospective study, PLoS Med., 13, e1002162, 10.1371/journal.pmed.1002162
Imielinski, 2014, Oncogenic and sorafenib-sensitive ARAF mutations in lung adenocarcinoma, J. Clin. Invest., 124, 1582, 10.1172/JCI72763
Stevers, 2018, Modulators of 14-3-3 protein-protein interactions, J. Med. Chem., 61, 3755, 10.1021/acs.jmedchem.7b00574
Yaffe, 1997, The structural basis for 14-3-3:phosphopeptide binding specificity, Cell, 91, 961, 10.1016/S0092-8674(00)80487-0
Shen, 2003, Significance of 14-3-3 self-dimerization for phosphorylation-dependent target binding, Mol. Biol. Cell, 14, 4721, 10.1091/mbc.e02-12-0821
Tzivion, 2002, 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation, J. Biol. Chem., 277, 3061, 10.1074/jbc.R100059200
Muslin, 1996, Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine, Cell, 84, 889, 10.1016/S0092-8674(00)81067-3
Morrison, 1993, Identification of the major phosphorylation sites of the Raf-1 kinase, J. Biol. Chem., 268, 17309, 10.1016/S0021-9258(19)85336-X
Roskoski, 2010, RAF protein-serine/threonine kinases: structure and regulation, Biochem. Biophys. Res. Commun., 399, 313, 10.1016/j.bbrc.2010.07.092
Alessi, 1994, Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1, EMBO J., 13, 1610, 10.1002/j.1460-2075.1994.tb06424.x
Roskoski, 2012, MEK1/2 dual-specificity protein kinases: structure and regulation, Biochem. Biophys. Res. Commun., 417, 5, 10.1016/j.bbrc.2011.11.145
Hatzivassiliou, 2010, RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth, Nature, 464, 431, 10.1038/nature08833
Yao, 2015, BRAF mutants evade ERK-dependent feedback by different mechanisms that determine their sensitivity to pharmacologic inhibition, Cancer Cell, 28, 370, 10.1016/j.ccell.2015.08.001
Yao, 2017, Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS, Nature, 548, 234, 10.1038/nature23291
Karoulia, 2016, An integrated model of RAF inhibitor action predicts inhibitor activity against oncogenic BRAF signaling, Cancer Cell, 30, 485, 10.1016/j.ccell.2016.06.024
Brown, 2009, Protein scaffolds in MAP kinase signalling, Cell. Signal., 21, 462, 10.1016/j.cellsig.2008.11.013
Morrison, 2003, Regulation of MAP kinase signaling modules by scaffold proteins in mammals, Ann. Rev. Cell Dev. Biol., 19, 91, 10.1146/annurev.cellbio.19.111401.091942
Liang, 2016, Scaffold proteins regulating extracellular regulated kinase function in cardiac hypertrophy and disease, Front. Pharmacol., 7, 37, 10.3389/fphar.2016.00037
Shaul, 2007, The MEK/ERK cascade: from signaling specificity to diverse functions, Biochim. Biophys. Acta, 1773, 1213, 10.1016/j.bbamcr.2006.10.005
Wortzel, 2011, The ERK cascade: distinct functions within various subcellular organelles, Genes Cancer, 2, 195, 10.1177/1947601911407328
Kornfeld, 1995, The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans, Cell, 83, 903, 10.1016/0092-8674(95)90206-6
Sundaram, 1995, The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction, Cell, 83, 889, 10.1016/0092-8674(95)90205-8
Therrien, 1995, KSR, a novel protein kinase required for RAS signal transduction, Cell, 83, 879, 10.1016/0092-8674(95)90204-X
Vomastek, 2004, Modular construction of a signaling scaffold: MORG1 interacts with components of the ERK cascade and links ERK signaling to specific agonists, Proc. Natl Acad. Sci. U.S.A., 101, 6981, 10.1073/pnas.0305894101
Schaeffer, 1998, MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade, Science, 281, 1668, 10.1126/science.281.5383.1668
Ishibe, 2003, Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis, Mol. Cell, 12, 1275, 10.1016/S1097-2765(03)00406-4
McDonald, 2000, β-Arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3, Science, 290, 1574, 10.1126/science.290.5496.1574
Karandikar, 2000, MEKK1 binds raf-1 and the ERK2 cascade components, J. Biol. Chem., 275, 40120, 10.1074/jbc.M005926200
Sheikh, 2008, An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice, J. Clin. Invest., 118, 3870, 10.1172/JCI34472
Roy, 2002, KSR is a scaffold required for activation of the ERK/MAPK module, Genes Dev., 16, 427, 10.1101/gad.962902
Ritt, 2006, KSR regulation of the Raf-MEK-ERK cascade, Methods Enzymol., 407, 224, 10.1016/S0076-6879(05)07019-9
Nguyen, 2002, Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo, Mol. Cell. Biol., 22, 3035, 10.1128/MCB.22.9.3035-3045.2002
Brennan, 2011, A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK, Nature, 472, 366, 10.1038/nature09860
Baljuls, 2016, Stabilization of C-RAF:KSR1 complex by DiRas3 reduces availability of C-RAF for dimerization with B-RAF, Cell Signal., 28, 1451, 10.1016/j.cellsig.2016.06.019
Anderson, 2006, Role of lipids in the MAPK signaling pathway, Prog. Lipid Res., 45, 102, 10.1016/j.plipres.2005.12.003
Yoon, 2006, The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions, Growth Factors, 24, 21, 10.1080/02699050500284218
Cseh, 2014, ‘RAF’ neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway, FEBS Lett., 588, 2398, 10.1016/j.febslet.2014.06.025
Blaževitš, 2016, Galectin-1 dimers can scaffold Raf-effectors to increase H-ras nanoclustering, Sci. Rep., 6, 24165, 10.1038/srep24165
Chen, 2001, Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism, Proc. Natl Acad. Sci. U.S.A., 98, 7783, 10.1073/pnas.141224398
Romano, 2014, Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling, Nat. Cell Biol., 16, 673, 10.1038/ncb2986