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Jin Q , Ding W , Staub CM , Gao G , Tang Q , Mulder KM
Requirement of km23 for TGF?-mediated growth inhibition and induction of fibronectin expression
Cellular Signalling. 2005 ;17(11) :1363-1372
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We previously identified km23 as a novel TGF? receptor-interacting protein. Here we show that km23 is ubiquitously expressed in human tissues and that cell-type specific differences in endogenous km23 protein expression exist. In addition, we demonstrate that the phosphorylation of km23 is TGF?-dependent, in that EGF was unable to phosphorylate km23. Further, the kinase activity of both TGF? receptors appears to play a role in the TGF?-mediated phosphorylation of km23, although TGF? RII kinase activity is absolutely required for km23 phosphorylation. Blockade of km23 using small interfering RNAs significantly decreased key TGF? responses, including induction of fibronectin expression and inhibition of cell growth. Thus, our results demonstrate that km23 is required for TGF? induction of fibronectin expression and is necessary, but not sufficient, for TGF?-mediated growth inhibition. © 2005 Elsevier Inc. All rights reserved.
08986568 (ISSN) Cited By: 2; Export Date: 25 May 2006; Source: Scopus CODEN: CESIE; DOI: 10.1016/j.cellsig.2005.02.004 Language of Original Document: English Correspondence Address: Mulder, K.M.; Department of Pharmacology; Pennsylvania State University; College of Medicine; 500 University Dr. Hershey, PA 17033, United States; email: kmm15@psu.edu Molecular Sequence Numbers: GENBANK: AAH46084, AF140239, AF141920, AJ243446, AQ850960, AY026513, M27999, Z54216; Chemicals/CAS: epidermal growth factor, 62229-50-9; fibronectin, 86088-83-7; phosphotransferase, 9031-09-8, 9031-44-1; protein, 67254-75-5, Dynein ATPase, EC; Epidermal Growth Factor, 62229-50-9; Fibronectins; Km23 protein, human, EC; Receptors, Transforming Growth Factor beta; RNA, Small Interfering; Transforming Growth Factor beta References: Yue, J., Mulder, K.M., (2001) Pharmacol. Ther., 91, p. 1; Derynck, R., Zhang, Y.E., (2003) Nature, 425, p. 577; Shi, Y.G., Massague, J., (2003) Cell, 113, p. 685; Akhurst, R.J., Derynck, R., (2001) Trends Cell Biol., 11, p. 44; Roberts, A.B., Wakefield, L.M., (2003) Proc. Natl. Acad. Sci. U. S. A., 100, p. 8621; Mehra, A., Wrana, J.L., (2002) Biochem. Cell. Biol., 80, p. 605; Mulder, K.M., (2000) Cytokine Growth Factor Rev., 11, p. 23; Ten Dijke, P., Goumans, M.J., Itoh, F., Itoh, S., (2002) J. Cell. Physiol., 191, p. 1; Danen, E.H.J., Yamada, K.M., (2001) J. Cell. Physiol., 189, p. 1; Pankov, R., Yamada, K.M., (2002) J. Cell Sci., 115, p. 3861; Massague, J., Blain, S.W., Lo, R.S., (2000) Cell, 103, p. 295; Roberts, A.B., Russo, A., Felici, A., Flanders, K.C., (2003) Ann. N. Y. Acad. Sci., 995, p. 1; Hocevar, B.A., Brown, T.L., Howe, P.H., (1999) EMBO J., 18, p. 1345; Gooch, J.L., Gorin, Y., Zhang, B.X., Abboud, H.E., (2004) J. Biol. Chem., 279, p. 15561; Tang, Q., Staub, C.M., Gao, G., Jin, Q., Wang, Z., Ding, W., Aurigemma, R.E., Mulder, K.M., (2002) Mol. Biol. Cell, 13, p. 4484; Zipfel, P.A., Ziober, B.L., Morris, S.L., Mulder, K.M., (1993) Cell Growth Differ., 4, p. 637; Yue, J., Frey, R.S., Mulder, K.M., (1999) Oncogene, 18, p. 2033; Yue, J., Hartsough, M.T., Frey, R.S., Frielle, T., Mulder, K.M., (1999) J. Cell. Physiol., 178, p. 387; Yue, J., Mulder, K.M., (2000) J. Biol. Chem., 275, p. 30765; Hartsough, M.T., Mulder, K.M., (1995) J. Biol. Chem., 270, p. 7117; Hoffmann, I., Draetta, G., Karsenti, E., (1994) EMBO J., 13, p. 4302; Dole, V., Jakubzik, C.R., Brunjes, B., Kreimer, G., (2000) Biochim. Biophys. Acta, 1490, p. 125; Akopyants, N.S., Clifton, S.W., Martin, J., Pape, D., Wylie, T., Li, L., Kissinger, J.C., (...), Beverley, S.M., (2001) Mol. Biochem. Parasitol., 113, p. 337; Mattaj, I.W., Englmeier, L., (1998) Annu. Rev. Biochem., 67, p. 265; Georgatos, S.D., Meier, J., Simos, G., (1994) Curr. Opin. Cell Biol., 6, p. 347; Jorissen, R.N., Walker, F., Pouliot, N., Garrett, T.P.J., Ward, C.W., Burgess, A.W., (2003) Exp. Cell Res., 284, p. 31; Sakaguchi, K., Okabayashi, Y., Kido, Y., Kimura, S., Matsumura, Y., Inushima, K., Kasuga, M., (1998) Mol. Endocrinol., 12, p. 536; Mao, W., Irby, R., Coppola, D., Fu, L., Wloch, M., Turner, J., Yu, H., (...), Yeatman, T.J., (1997) Oncogene, 15, p. 3083; David, M., Wong, L., Flavell, R., Thompson, S.A., Wells, A., Larner, A.C., Johnson, G.R., (1996) J. Biol. Chem., 271, p. 9185; Wahl, M.I., Nishibe, S., Kim, J.W., Kim, H., Rhee, S.G., Carpenter, G., (1990) J. Biol. Chem., 265, p. 3944; Camp, H.S., Tafuri, S.R., (1997) J. Biol. Chem., 272, p. 10811; Laiho, M., Decaprio, J.A., Ludlow, J.W., Livingston, D.M., Massague, J., (1990) Cell, 62, p. 175; Ignotz, R.A., Massague, J., (1986) J. Biol. Chem., 261, p. 4337; Wrana, J.L., Overall, C.M., Sodek, J., (1991) Eur. J. Biochem., 197, p. 519; Mulder, K.M., Morris, S.L., (1992) J. Biol. Chem., 267, p. 5029; Hartsough, M.T., Frey, R.S., Zipfel, P.A., Buard, A., Cook, S.J., McCormick, F., Mulder, K.M., (1996) J. Biol. Chem., 271, p. 22368; Yue, J., Buard, A., Mulder, K.M., (1998) Oncogene, 17, p. 47; Frey, R.S., Mulder, K.M., (1997) Cancer Res., 57, p. 628; Sovak, M.A., Arsura, M., Zanieski, G., Kavanagh, K.T., Sonenshein, G.E., (1999) Cell Growth Differ., 10, p. 537.