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Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf1

dc.contributor.authorLanigan, Thomas M.
dc.contributor.authorLiu, Albert
dc.contributor.authorHuang, Yang Z.
dc.contributor.authorMei, Lin
dc.contributor.authorMargolis, Ben
dc.contributor.authorGuan, Kun-Liang
dc.date.accessioned2020-03-17T18:28:05Z
dc.date.available2020-03-17T18:28:05Z
dc.date.issued2003-11
dc.identifier.citationLanigan, Thomas M.; Liu, Albert; Huang, Yang Z.; Mei, Lin; Margolis, Ben; Guan, Kun-Liang (2003). "Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf1." The FASEB Journal 17(14): 2048-2060.
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.urihttps://hdl.handle.net/2027.42/154294
dc.description.abstractConnector enhancer of KSR (CNK) is a multidomain protein that participates in Ras signaling in Drosophila eye development. In this report we identify the human homologue of CNK, termed CNK2A, and a truncated alternatively spliced variant, CNK2B. We characterize CNK2 phosphorylation, membrane localization, and interaction with Ras effector molecules. Our results show that MAPK signaling appears to play a role in the phosphorylation of CNK2 in vivo. CNK2 is found in both membrane and cytoplasmic fractions of the cell. In MDCK cells, full‐length CNK2 is localized to the lateral plasma membrane. Consistent with previous reports, we show CNK2 interacts with Raf. CNK2 interaction was mapped to the regulatory and kinase domains of Raf, as well as to the carboxyl‐terminal half of CNK2. CNK2 also interacts with the Ral signaling components, Ral GTPase, and the Ral‐GDS family member Rlf. CNK2 interaction was mapped to the GEF domain of Rlf. The ability of CNK2 to interact with both Ras effector proteins Raf and Rlf suggests that CNK2 may integrate signals between MAPK and Ral pathways through a complex interplay of components.—Lanigan T. M., Liu A., Huang Y. Z., Mei L., Margolis B., Guan K.‐L. Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. FASEB J. 17, 2048–2060 (2003)
dc.publisherWiley Periodicals, Inc.
dc.titleHuman homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf1
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelBiology
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154294/1/fsb2fj021096com.pdf
dc.identifier.doi10.1096/fj.02-1096com
dc.identifier.sourceThe FASEB Journal
dc.identifier.citedreferenceJullien-Flores, V., Dorseuil, O., Romero, F., Letourneur, F., Saragosti, S., Berger, R., Tavitian, A., Gacon, G., and Camonis, J. H. ( 1995 ) Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity. J. Biol. Chem. 270, 22473 – 22477
dc.identifier.citedreferenceWolthuis, R. M., de Ruiter, N. D., Cool, R. H., and Bos, J. L. ( 1997 ) Stimulation of gene induction and cell growth by the Ras effector Rlf. EMBO J. 16, 6748 – 6761
dc.identifier.citedreferenceWolthuis, R. M., Bauer, B., van’t Veer, L. J., de Vries-Smits, A. M., and Cool, R. H., Spaargaren, M., Wittinghofer, A., Burgering, B. M., and Bos, J. L. ( 1996 ) RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein. Oncogene 13, 353 – 362
dc.identifier.citedreferenceHu, P., Mondino, A., Skolnik, E. Y., and Schlessinger, J. ( 1993 ) Cloning of a novel, ubiquitously expressed human phosphati-dylinositol 3-kinase and identification of its binding site on p85. Mol. Cell. Biol. 13, 7677 – 7688
dc.identifier.citedreferenceWaters, S. B., Chen, D., Kao, A. W., Okada, S., Holt, K. H., and Pessin, J. E. ( 1996 ) Insulin and epidermal growth factor receptors regulate distinct pools of Grb2-SOS in the control of Ras activation. J. Biol. Chem. 271, 18224 – 18230
dc.identifier.citedreferenceTang, E. D., Nunez, G., Barr, F. G., and Guan, K. L. ( 1999 ) Negative regulation of the forkhead transcription factor FKHR by Akt. J. Biol. Chem. 274, 16741 – 16746
dc.identifier.citedreferenceZheng, C. F., and Guan, K. L. ( 1994 ) Cytoplasmic localization of the mitogen-activated protein kinase activator MEK. J. Biol. Chem. 269, 19947 – 19952
dc.identifier.citedreferenceWolthuis, R. M., Franke, B., van Triest, M., Bauer, B., Cool, R. H., Camonis, J. H., Akkerman, J. W., and Bos, J. L. ( 1998 ) Activation of the small GTPase Ral in platelets. Mol. Cell. Biol. 18, 2486 – 2491
dc.identifier.citedreferenceHuang, Y. Z., Won, S., Ali, D. W., Wang, Q., Tanowitz, M., Du, Q. S., Pelkey, K. A., Yang, D. J., Xiong, W. C., Salter, M. W., et al. ( 2000 ) Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses. Neuron 26, 443 – 455
dc.identifier.citedreferenceMuller, J., Ory, S., Copeland, T., Piwnica-Worms, H., and Morrison, D. K. ( 2001 ) C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1. Mol. Cell 8, 983 – 993
dc.identifier.citedreferenceCacace, A. M., Michaud, N. R., Therrien, M., Mathes, K., Copeland, T., Rubin, G. M., and Morrison, D. K. ( 1999 ) Identification of constitutive and ras-inducible phosphorylation sites of KSR: implications for 14–3-3 binding, mitogen-activated protein kinase binding, and KSR overexpression. Mol. Cell. Biol. 19, 229 – 240
dc.identifier.citedreferenceDenouel-Galy, A., Douville, E. M., Warne, P. H., Papin, C., Laugier, D., Calothy, G., Downward, J., and Eychene, A. ( 1998 ) Murine Ksr interacts with MEK and inhibits Ras-induced transformation. Curr. Biol. 8, 46 – 55
dc.identifier.citedreferenceJoneson, T., Fulton, J. A., Volle, D. J., Chaika, O. V., Bar-Sagi, D., and Lewis, R. E. ( 1998 ) Kinase suppressor of Ras inhibits the activation of extracellular ligand-regulated (ERK) mitogen-activated protein (MAP) kinase by growth factors, activated Ras, and Ras effectors. J. Biol. Chem. 273, 7743 – 7748
dc.identifier.citedreferenceYu, W., Fantl, W. J., Harrowe, G., and Williams, L. T. ( 1998 ) Regulation of the MAP kinase pathway by mammalian Ksr through direct interaction with MEK and ERK. Curr. Biol. 8, 56 – 64
dc.identifier.citedreferenceDickens, M., Rogers, J. S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J. R., Greenberg, M. E., Sawyers, C. L., and Davis, R. J. ( 1997 ) A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 277, 693 – 696
dc.identifier.citedreferenceWhitmarsh, A. J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R. J. ( 1998 ) A mammalian scaffold complex that selectively mediates MAP kinase activation. Science 281, 1671 – 1674
dc.identifier.citedreferenceRoy, F., Laberge, G., Douziech, M., Ferland-McCollough, D., and Therrien, M. ( 2002 ) KSR is a scaffold required for activation of the ERK/MAPK module. Genes Dev. 16, 427 – 438
dc.identifier.citedreferenceVerheijen, M. H., Wolthuis, R. M., Defize, L. H., den Hertog, J., and Bos, J. L. ( 1999 ) Interdependent action of RalGEF and Erk in Ras-induced primitive endoderm differentiation of F9 embryonal carcinoma cells. Oncogene 18, 4435 – 4439
dc.identifier.citedreferenceProber, D. A., and Edgar, B. A. ( 2002 ) Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Genes Dev. 16, 2286 – 2299
dc.identifier.citedreferenceMirey, G., Balakireva, M., L’Hoste, S., Rosse, C., Voegeling, S., and Camonis, J. ( 2003 ) A Ral guanine exchange factor-Ral pathway is conserved in Drosophila melanogaster and sheds new light on the connectivity of the Ral, Ras, and Rap pathways. Mol. Cell. Biol. 23, 1112 – 1124
dc.identifier.citedreferenceBos, J. L. ( 1998 ) All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral. EMBO J. 17, 6776 – 6782
dc.identifier.citedreferenceKatz, M. E., and McCormick, F. ( 1997 ) Signal transduction from multiple Ras effectors. Curr. Opin. Genet. Dev. 7, 75 – 79
dc.identifier.citedreferenceSundaram, M., and Han, M. ( 1996 ) Control and integration of cell signaling pathways during C. elegans vulval development. Bioessays 18, 473 – 480
dc.identifier.citedreferenceWassarman, D. A., Therrien, M., and Rubin, G. M. ( 1995 ) The Ras signaling pathway in Drosophila. Curr. Opin. Genet. Dev. 5, 44 – 50
dc.identifier.citedreferenceKornfeld, K., Hom, D. B., and Horvitz, H. R. ( 1995 ) The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans. Cell 83, 903 – 913
dc.identifier.citedreferenceSundaram, M., and Han, M. ( 1995 ) The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction. Cell 83, 889 – 901
dc.identifier.citedreferenceTherrien, M., Chang, H. C., Solomon, N. M., Karim, F. D., Wassarman, D. A., and Rubin, G. M. ( 1995 ) KSR, a novel protein kinase required for RAS signal transduction. Cell 83, 879 – 888
dc.identifier.citedreferenceMichaud, N. R., Therrien, M., Cacace, A., Edsall, L. C., Spiegel, S., Rubin, G. M., and Morrison, D. K. ( 1997 ) KSR stimulates Raf-1 activity in a kinase-independent manner. Proc. Natl. Acad. Sci. USA 94, 12792 – 12796
dc.identifier.citedreferenceMorrison, D. K. ( 2001 ) KSR: a MAPK scaffold of the Ras pathway? J. Cell Sci. 114, 1609 – 1612
dc.identifier.citedreferenceStewart, S., Sundaram, M., Zhang, Y., Lee, J., Han, M., and Guan, K. L. ( 1999 ) Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization. Mol. Cell. Biol. 19, 5523 – 5534
dc.identifier.citedreferenceXing, H., Kornfeld, K., and Muslin, A. J. ( 1997 ) The protein kinase KSR interacts with 14-3-3 protein and Raf. Curr. Biol. 7, 294 – 300
dc.identifier.citedreferenceSieburth, D. S., Sun, Q., and Han, M. ( 1998 ) SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in C. elegans. Cell 94, 119 – 130
dc.identifier.citedreferenceLi, W., Han, M., and Guan, K. L. ( 2000 ) The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf. Genes Dev. 14, 895 – 900
dc.identifier.citedreferenceSchaeffer, H.J., Catling, A. D., Eblen, S. T., Collier, L. S., Krauss, A., and Weber, M.J. ( 1998 ) MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science 281, 1668 – 1671
dc.identifier.citedreferenceTherrien, M., Wong, A. M., and Rubin, G. M. ( 1998 ) CNK, a RAF-binding multidomain protein required for RAS signaling. Cell 95, 343 – 353
dc.identifier.citedreferenceAnselmo, A. N., Bumeister, R., Thomas, J. M., and White, M. A. ( 2002 ) Critical contribution of linker proteins to Raf kinase activation. J. Biol. Chem. 277, 5940 – 5943
dc.identifier.citedreferenceTherrien, M., Wong, A. M., Kwan, E., and Rubin, G. M. ( 1999 ) Functional analysis of CNK in RAS signaling. Proc. Natl. Acad. Sci. USA 96, 13259 – 13263
dc.identifier.citedreferenceWhite, M. A., Nicolette, C., Minden, A., Polverino, A., Van Aelst, L., Karin, M., and Wigler, M. H. ( 1995 ) Multiple Ras functions can contribute to mammalian cell transformation. Cell 80, 533 – 541
dc.identifier.citedreferenceRodriguez-Viciana, P., Warne, P. H., Khwaja, A., Marte, B. M., Pappin, D., Das, P., Waterfield, M. D., Ridley, A., and Downward, J. ( 1997 ) Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras. Cell 89, 457 – 467
dc.identifier.citedreferenceYao, I., Hata, Y., Ide, N., Hirao, K., Deguchi, M., Nishioka, H., Mizoguchi, A., and Takai, Y. ( 1999 ) MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting protein. J. Biol. Chem. 274, 11889 – 11896
dc.identifier.citedreferenceYao, I., Ohtsuka, T., Kawabe, H., Matsuura, Y., Takai, Y., and Hata, Y. ( 2000 ) Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1. Biochem. Biophys. Res. Commun. 270, 538 – 542
dc.identifier.citedreferenceSugimoto, T., Stewart, S., Han, M., and Guan, K. L. ( 1998 ) The kinase suppressor of Ras (KSR) modulates growth factor and Ras signaling by uncoupling Elk-1 phosphorylation from MAP kinase activation. EMBO J. 17, 1717 – 1727
dc.identifier.citedreferenceTang, E. D., Nunez, G., Barr, F. G., and Guan, K. L. ( 1999 ) Negative regulation of the forkhead transcription factor FKHR by Akt. J. Biol. Chem. 274, 16741 – 16746
dc.identifier.citedreferenceGuan, K. L., and Dixon, J. E. ( 1991 ) Eukaryotic proteins expressed in Escherichia coli: an improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase. Anal. Biochem. 192, 262 – 267
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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