Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation

doi:10.1083/jcb.200102032

Published online 16 July 2001. doi:10.1083/jcb.200102032

This Article

	Full Text
	PDF (Full Text)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Grimm, J.
	Articles by Birchmeier, W.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Grimm, J.
	Articles by Birchmeier, W.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/2001/7/345 $5.00
The Journal of Cell Biology, Volume 154, Number 2, July 23, 2001 345-354

Article

Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation

Jan Grimm¹, Martin Sachs¹, Stefan Britsch¹, Silvana Di Cesare¹, Thomas Schwarz-Romond¹, Kari Alitalo² and Walter Birchmeier¹

¹ Max-Delbrueck-Center for Molecular Medicine, 13092 Berlin, Germany
² Molecular/Cancer Biology Laboratory, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland

Address correspondence to W. Birchmeier, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13092 Berlin, Germany. Tel.: (49) 309-406-3800. Fax: (49) 309-406-2656. E-mail: wbirch{at}mdc-berlin.de

Docking proteins are substrates of tyrosine kinases and functionin the recruitment and assembly of specific signal transductionmolecules. Here we found that p62dok family members act as substratesfor the c-Ret receptor tyrosine kinase. In addition to dok-1,dok-2, and dok-3, we identified two new family members, dok-4and dok-5, that can directly associate with Y1062 of c-Ret.Dok-4 and dok-5 constitute a subgroup of dok family membersthat is coexpressed with c-Ret in various neuronal tissues.Activated c-Ret promotes neurite outgrowth of PC12 cells; forthis activity, Y1062 in c-Ret is essential. c-Ret/dok fusionproteins, in which Y1062 of c-Ret is deleted and replaced bythe sequences of dok-4 or dok-5, induce ligand-dependent axonaloutgrowth of PC12 cells, whereas a c-Ret fusion containing dok-2sequences does not elicit this response. Dok-4 and dok-5 donot associate with rasGAP or Nck, in contrast to p62dok anddok-2. Moreover, dok-4 and dok-5 enhance c-Ret–dependentactivation of mitogen-activated protein kinase. Thus, we haveidentified a subclass of p62dok proteins that are putative linkswith downstream effectors of c-Ret in neuronal differentiation.

Key Words: signal transduction; yeast two-hybrid system; docking proteins; neural development; endothelia

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Boulay, A., Breuleux, M., Stephan, C., Fux, C., Brisken, C., Fiche, M., Wartmann, M., Stumm, M., Lane, H. A., Hynes, N. E. (2008). The Ret Receptor Tyrosine Kinase Pathway Functionally Interacts with the ER{alpha} Pathway in Breast Cancer. Cancer Res. 68: 3743-3751 [Abstract] [Full Text]
Oxley, C. L., Anthis, N. J., Lowe, E. D., Vakonakis, I., Campbell, I. D., Wegener, L. (2008). An Integrin Phosphorylation Switch: THE EFFECT OF {beta}3 INTEGRIN TAIL PHOSPHORYLATION ON DOK1 AND TALIN BINDING. J. Biol. Chem. 283: 5420-5426 [Abstract] [Full Text]
Hamuro, J., Higuchi, O., Okada, K., Ueno, M., Iemura, S.-i., Natsume, T., Spearman, H., Beeson, D., Yamanashi, Y. (2008). Mutations Causing DOK7 Congenital Myasthenia Ablate Functional Motifs in Dok-7. J. Biol. Chem. 283: 5518-5524 [Abstract] [Full Text]
Schaeper, U., Vogel, R., Chmielowiec, J., Huelsken, J., Rosario, M., Birchmeier, W. (2007). Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo. Proc. Natl. Acad. Sci. USA 104: 15376-15381 [Abstract] [Full Text]
Inoue, A., Yasuda, T., Yamamoto, T., Yamanashi, Y. (2007). Dok-1 is a Positive Regulator of IL-4 Signalling and IgE Response. J Biochem 142: 257-263 [Abstract] [Full Text]
Ng, C.-H., Xu, S., Lam, K.-P. (2007). Dok-3 plays a nonredundant role in negative regulation of B-cell activation. Blood 110: 259-266 [Abstract] [Full Text]
Matsubara, Y., Kawasaki, I., Urushiyama, S., Yasuda, T., Shirakata, M., Iino, Y., Shibuya, H., Yamanashi, Y. (2007). The adaptor-like protein ROG-1 is required for activation of the Ras-MAP kinase pathway and meiotic cell cycle progression in Caenorhabditis elegans. GENES CELLS 12: 407-420 [Abstract] [Full Text]
Smith, M. J., Hardy, W. R., Murphy, J. M., Jones, N., Pawson, T. (2006). Screening for PTB Domain Binding Partners and Ligand Specificity Using Proteome-Derived NPXY Peptide Arrays. Mol. Cell. Biol. 26: 8461-8474 [Abstract] [Full Text]
Lundgren, T. K., Scott, R. P., Smith, M., Pawson, T., Ernfors, P. (2006). Engineering the Recruitment of Phosphotyrosine Binding Domain-containing Adaptor Proteins Reveals Distinct Roles for RET Receptor-mediated Cell Survival. J. Biol. Chem. 281: 29886-29896 [Abstract] [Full Text]
de Groot, J. W. B., Links, T. P., Plukker, J. T. M., Lips, C. J. M., Hofstra, R. M. W. (2006). RET as a Diagnostic and Therapeutic Target in Sporadic and Hereditary Endocrine Tumors. Endocr. Rev. 27: 535-560 [Abstract] [Full Text]
Uchida, M., Enomoto, A., Fukuda, T., Kurokawa, K., Maeda, K., Kodama, Y., Asai, N., Hasegawa, T., Shimono, Y., Jijiwa, M., Ichihara, M., Murakumo, Y., Takahashi, M. (2006). Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase. J. Cell Sci. 119: 3067-3077 [Abstract] [Full Text]
Cabrera, J. R., Sanchez-Pulido, L., Rojas, A. M., Valencia, A., Manes, S., Naranjo, J. R., Mellstrom, B. (2006). Gas1 Is Related to the Glial Cell-derived Neurotrophic Factor Family Receptors {alpha} and Regulates Ret Signaling. J. Biol. Chem. 281: 14330-14339 [Abstract] [Full Text]
Zhang, Y., Zhu, W., Wang, Y.-G., Liu, X.-J., Jiao, L., Liu, X., Zhang, Z.-H., Lu, C.-L., He, C. (2006). Interaction of SH2-B{beta} with RET is involved in signaling of GDNF-induced neurite outgrowth. J. Cell Sci. 119: 1666-1676 [Abstract] [Full Text]
Zhao, M., Janas, J. A., Niki, M., Pandolfi, P. P., Van Aelst, L. (2006). Dok-1 Independently Attenuates Ras/Mitogen-Activated Protein Kinase and Src/c-Myc Pathways To Inhibit Platelet-Derived Growth Factor-Induced Mitogenesis.. Mol. Cell. Biol. 26: 2479-2489 [Abstract] [Full Text]
Honma, M., Higuchi, O., Shirakata, M., Yasuda, T., Shibuya, H., Iemura, S.-i., Natsume, T., Yamanashi, Y. (2006). Dok-3 sequesters Grb2 and inhibits the Ras-Erk pathway downstream of protein-tyrosine kinases. GENES CELLS 11: 143-151 [Abstract] [Full Text]
Biswas, R., Stein, D., Stanley, E. R. (2006). Drosophila Dok is required for embryonic dorsal closure. Development 133: 217-227 [Abstract] [Full Text]
Wong, A., Bogni, S., Kotka, P., de Graaff, E., D'Agati, V., Costantini, F., Pachnis, V. (2005). Phosphotyrosine 1062 Is Critical for the In Vivo Activity of the Ret9 Receptor Tyrosine Kinase Isoform. Mol. Cell. Biol. 25: 9661-9673 [Abstract] [Full Text]
Boulay, I., Nemorin, J.-G., Duplay, P. (2005). Phosphotyrosine Binding-Mediated Oligomerization of Downstream of Tyrosine Kinase (Dok)-1 and Dok-2 Is Involved in CD2-Induced Dok Phosphorylation. J. Immunol. 175: 4483-4489 [Abstract] [Full Text]
Itoh, S., Lemay, S., Osawa, M., Che, W., Duan, Y., Tompkins, A., Brookes, P. S., Sheu, S.-S., Abe, J.-i. (2005). Mitochondrial Dok-4 Recruits Src Kinase and Regulates NF-{kappa}B Activation in Endothelial Cells. J. Biol. Chem. 280: 26383-26396 [Abstract] [Full Text]
Van Slyke, P., Coll, M. L., Master, Z., Kim, H., Filmus, J., Dumont, D. J. (2005). Dok-R Mediates Attenuation of Epidermal Growth Factor-Dependent Mitogen-Activated Protein Kinase and Akt Activation through Processive Recruitment of c-Src and Csk. Mol. Cell. Biol. 25: 3831-3841 [Abstract] [Full Text]
Sekine, Y., Yamamoto, T., Yumioka, T., Sugiyama, K., Tsuji, S., Oritani, K., Shimoda, K., Minoguchi, M., Yoshimura, A., Matsuda, T. (2005). Physical and Functional Interactions between STAP-2/BKS and STAT5. J. Biol. Chem. 280: 8188-8196 [Abstract] [Full Text]
Niki, M., Di Cristofano, A., Zhao, M., Honda, H., Hirai, H., Van Aelst, L., Cordon-Cardo, C., Pandolfi, P. P. (2004). Role of Dok-1 and Dok-2 in Leukemia Suppression. J. Exp. Med. 200: 1689-1695 [Abstract] [Full Text]
Lee, S., Andrieu, C., Saltel, F., Destaing, O., Auclair, J., Pouchkine, V., Michelon, J., Salaun, B., Kobayashi, R., Jurdic, P., Kieff, E. D., Sylla, B. S. (2004). I{kappa}B kinase {beta} phosphorylates Dok1 serines in response to TNF, IL-1, or {gamma} radiation. Proc. Natl. Acad. Sci. USA 101: 17416-17421 [Abstract] [Full Text]
Schuetz, G., Rosario, M., Grimm, J., Boeckers, T. M., Gundelfinger, E. D., Birchmeier, W. (2004). The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells. J. Cell Biol. 167: 945-952 [Abstract] [Full Text]
Crowder, R. J., Enomoto, H., Yang, M., Johnson, E. M. Jr., Milbrandt, J. (2004). Dok-6, a Novel p62 Dok Family Member, Promotes Ret-mediated Neurite Outgrowth. J. Biol. Chem. 279: 42072-42081 [Abstract] [Full Text]
Jijiwa, M., Fukuda, T., Kawai, K., Nakamura, A., Kurokawa, K., Murakumo, Y., Ichihara, M., Takahashi, M. (2004). A Targeting Mutation of Tyrosine 1062 in Ret Causes a Marked Decrease of Enteric Neurons and Renal Hypoplasia. Mol. Cell. Biol. 24: 8026-8036 [Abstract] [Full Text]
Myers, S. M., Mulligan, L. M. (2004). The RET Receptor Is Linked to Stress Response Pathways. Cancer Res. 64: 4453-4463 [Abstract] [Full Text]
Woodring, P. J., Meisenhelder, J., Johnson, S. A., Zhou, G.-L., Field, J., Shah, K., Bladt, F., Pawson, T., Niki, M., Pandolfi, P. P., Wang, J. Y.J., Hunter, T. (2004). c-Abl phosphorylates Dok1 to promote filopodia during cell spreading. J. Cell Biol. 165: 493-503 [Abstract] [Full Text]
Encinas, M., Crowder, R. J., Milbrandt, J., Johnson, E. M. Jr. (2004). Tyrosine 981, a Novel Ret Autophosphorylation Site, Binds c-Src to Mediate Neuronal Survival. J. Biol. Chem. 279: 18262-18269 [Abstract] [Full Text]
Bedirian, A., Baldwin, C., Abe, J.-i., Takano, T., Lemay, S. (2004). Pleckstrin Homology and Phosphotyrosine-binding Domain-dependent Membrane Association and Tyrosine Phosphorylation of Dok-4, an Inhibitory Adapter Molecule Expressed in Epithelial Cells. J. Biol. Chem. 279: 19335-19349 [Abstract] [Full Text]
Wang, X., Seed, B. (2003). A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res 31: e154-e154 [Abstract] [Full Text]
Cheng, H.-T., Miner, J. H., Lin, M., Tansey, M. G., Roth, K., Kopan, R. (2003). {gamma}-Secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney. Development 130: 5031-5042 [Abstract] [Full Text]
Cai, D., Dhe-Paganon, S., Melendez, P. A., Lee, J., Shoelson, S. E. (2003). Two New Substrates in Insulin Signaling, IRS5/DOK4 and IRS6/DOK5. J. Biol. Chem. 278: 25323-25330 [Abstract] [Full Text]
Minoguchi, M., Minoguchi, S., Aki, D., Joo, A., Yamamoto, T., Yumioka, T., Matsuda, T., Yoshimura, A. (2003). STAP-2/BKS, an Adaptor/Docking Protein, Modulates STAT3 Activation in Acute-phase Response through Its YXXQ Motif. J. Biol. Chem. 278: 11182-11189 [Abstract] [Full Text]
Pelicci, G., Troglio, F., Bodini, A., Melillo, R. M., Pettirossi, V., Coda, L., De Giuseppe, A., Santoro, M., Pelicci, P. G. (2002). The Neuron-Specific Rai (ShcC) Adaptor Protein Inhibits Apoptosis by Coupling Ret to the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway. Mol. Cell. Biol. 22: 7351-7363 [Abstract] [Full Text]
Tsui-Pierchala, B. A., Ahrens, R. C., Crowder, R. J., Milbrandt, J., Johnson, E. M. Jr. (2002). The Long and Short Isoforms of Ret Function as Independent Signaling Complexes. J. Biol. Chem. 277: 34618-34625 [Abstract] [Full Text]
Murakami, H., Yamamura, Y., Shimono, Y., Kawai, K., Kurokawa, K., Takahashi, M. (2002). Role of Dok1 in Cell Signaling Mediated by RET Tyrosine Kinase. J. Biol. Chem. 277: 32781-32790 [Abstract] [Full Text]
Gugasyan, R., Quilici, C., I, S. T.T., Grail, D., Verhagen, A. M., Roberts, A., Kitamura, T., Dunn, A. R., Lock, P. (2002). Dok-related protein negatively regulates T cell development via its RasGTPase-activating protein and Nck docking sites. J. Cell Biol. 158: 115-125 [Abstract] [Full Text]
Lock, L. S., Maroun, C. R., Naujokas, M. A., Park, M. (2002). Distinct Recruitment and Function of Gab1 and Gab2 in Met Receptor-mediated Epithelial Morphogenesis. Mol. Biol. Cell 13: 2132-2146 [Abstract] [Full Text]
Fukuda, T., Kiuchi, K., Takahashi, M. (2002). Novel Mechanism of Regulation of Rac Activity and Lamellipodia Formation by RET Tyrosine Kinase. J. Biol. Chem. 277: 19114-19121 [Abstract] [Full Text]
Coulpier, M., Anders, J., Ibanez, C. F. (2002). Coordinated Activation of Autophosphorylation Sites in the RET Receptor Tyrosine Kinase. IMPORTANCE OF TYROSINE 1062 FOR GDNF MEDIATED NEURONAL DIFFERENTIATION AND SURVIVAL. J. Biol. Chem. 277: 1991-1999 [Abstract] [Full Text]