Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention Tumor Immunology: New Perspectives
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gabriella De Vita,
Right arrow Articles by Santoro, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gabriella De Vita,
Right arrow Articles by Santoro, M.
[Cancer Research 60, 3727-3731, July 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Tyrosine 1062 of RET-MEN2A Mediates Activation of Akt (Protein Kinase B) and Mitogen-activated Protein Kinase Pathways Leading to PC12 Cell Survival1

Gabriella De Vita, Rosa Marina Melillo, Francesca Carlomagno, Roberta Visconti, Maria Domenica Castellone, Alfonso Bellacosa, Marc Billaud, Alfredo Fusco, Philip N. Tsichlis and Massimo Santoro2

Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare, 80131 Naples, Italy [G. D. V., R. M. M., F. C., R. V., M. D. C., M. S.]; Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; Catholic University, Medical School, 00168 Rome, Italy [A. B.]; Laboratoire de Génétique, Centre National de la Recherche Scientifique UMR5641, Lyon 69373 Cedex 08, France [M. B.]; Dipartimento di Medicina Sperimentale e Clinica, Catanzaro, Italy [ A. F.]; and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [P. N. T.]

The RET tyrosine kinase is a functional receptor for neurotrophic ligands of the glial cell line-derived neurotrophic factor (GDNF) family. Loss of function of RET is associated with congenital megacolon or Hirschsprung’s disease, whereas germ-line point mutations causing RET activation are responsible for multiple endocrine neoplasia type 2 (MEN2A, MEN2B, and familial medullary thyroid carcinoma) syndromes. Here we show that the expression of a constitutively active RET-MEN2A oncogene promotes survival of rat pheochromocytoma PC12 cells upon growth factor withdrawal. Moreover, we show that the RET-MEN2A-mediated survival depends on signals transduced by the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) cascades. Thus, in PC12 cells, RET-MEN2A associates with the PI3K regulatory subunit p85 and promotes activation of Akt (also referred to as protein kinase B) in a PI3K-dependent fashion; in addition, RET-MEN2A promotes MAPK activation. PI3K recruitment and Akt activation as well as MAPK activation depend on RET-MEN2A tyrosine residue 1062. As a result, tyrosine 1062 of RET-MEN2A is essential for RET-MEN2A-mediated survival of PC12 cells cultured in growth factor-depleted media.




This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
H. S. Jung, D. W. Kim, Y. S. Jo, H. K. Chung, J. H. Song, J. S. Park, K. C. Park, S. H. Park, J. H. Hwang, K.-W. Jo, et al.
Regulation of Protein Kinase B Tyrosine Phosphorylation by Thyroid-Specific Oncogenic RET/PTC Kinases
Mol. Endocrinol., November 1, 2005; 19(11): 2748 - 2759.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Fassnacht, D. Weismann, S. Ebert, P. Adam, M. Zink, F. Beuschlein, S. Hahner, and B. Allolio
AKT Is Highly Phosphorylated in Pheochromocytomas But Not in Benign Adrenocortical Tumors
J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4366 - 4370.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Y. Osajima-Hakomori, I. Miyake, M. Ohira, A. Nakagawara, A. Nakagawa, and R. Sakai
Biological Role of Anaplastic Lymphoma Kinase in Neuroblastoma
Am. J. Pathol., July 1, 2005; 167(1): 213 - 222.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. C. Zatelli, D. Piccin, F. Tagliati, A. Bottoni, A. Luchin, and E. C. degli Uberti
Src Homology-2-Containing Protein Tyrosine Phosphatase-1 Restrains Cell Proliferation in Human Medullary Thyroid Carcinoma
Endocrinology, June 1, 2005; 146(6): 2692 - 2698.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
J A Fagin
How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy
J. Endocrinol., November 1, 2004; 183(2): 249 - 256.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Chiara, M.-J. Goumans, H. Forsberg, A. Ahgren, A. Rasola, P. Aspenstrom, C. Wernstedt, C. Hellberg, C.-H. Heldin, and R. Heuchel
A Gain of Function Mutation in the Activation Loop of Plateletderived Growth Factor {beta}-Receptor Deregulates Its Kinase Activity
J. Biol. Chem., October 8, 2004; 279(41): 42516 - 42527.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Jijiwa, T. Fukuda, K. Kawai, A. Nakamura, K. Kurokawa, Y. Murakumo, M. Ichihara, and M. Takahashi
A Targeting Mutation of Tyrosine 1062 in Ret Causes a Marked Decrease of Enteric Neurons and Renal Hypoplasia
Mol. Cell. Biol., September 15, 2004; 24(18): 8026 - 8036.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. M. Myers and L. M. Mulligan
The RET Receptor Is Linked to Stress Response Pathways
Cancer Res., July 1, 2004; 64(13): 4453 - 4463.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
V Vasko, M Saji, E Hardy, M Kruhlak, A Larin, V Savchenko, M Miyakawa, O Isozaki, H Murakami, T Tsushima, et al.
Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer
J. Med. Genet., March 1, 2004; 41(3): 161 - 170.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
H.-T. Cheng, J. H. Miner, M. Lin, M. G. Tansey, K. Roth, and R. Kopan
{gamma}-Secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney
Development, October 15, 2003; 130(20): 5031 - 5042.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. D'Alessio, D. Califano, M. Incoronato, G. Santelli, T. Florio, G. Schettini, M. S. Carlomagno, L. Cerchia, and V. de Franciscis
The Tyrosine Phosphatase Shp-2 Mediates Intracellular Signaling Initiated by Ret Mutants
Endocrinology, October 1, 2003; 144(10): 4298 - 4305.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Wang, J. A. Knauf, S. Basu, E. Puxeddu, H. Kuroda, M. Santoro, A. Fusco, and J. A. Fagin
Conditional Expression of RET/PTC Induces a Weak Oncogenic Drive in Thyroid PCCL3 Cells and Inhibits Thyrotropin Action at Multiple Levels
Mol. Endocrinol., July 1, 2003; 17(7): 1425 - 1436.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. Natarajan, C. Marcos-Gutierrez, V. Pachnis, and E. de Graaff
Requirement of signalling by receptor tyrosine kinase RET for the directed migration of enteric nervous system progenitor cells during mammalian embryogenesis
Development, March 13, 2003; 129(22): 5151 - 5160.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
G. Pelicci, F. Troglio, A. Bodini, R. M. Melillo, V. Pettirossi, L. Coda, A. De Giuseppe, M. Santoro, and P. G. Pelicci
The Neuron-Specific Rai (ShcC) Adaptor Protein Inhibits Apoptosis by Coupling Ret to the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway
Mol. Cell. Biol., October 15, 2002; 22(20): 7351 - 7363.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
J. F. POWERS, K. H. SCHELLING, J. M. BRACHOLD, and A. S. TISCHLER
Plasticity of Pheochromocytoma Cell Lines from Neurofibromatosis Knockout Mice
Ann. N.Y. Acad. Sci., October 1, 2002; 971(1): 371 - 378.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. A. Tsui-Pierchala, R. C. Ahrens, R. J. Crowder, J. Milbrandt, and E. M. Johnson Jr.
The Long and Short Isoforms of Ret Function as Independent Signaling Complexes
J. Biol. Chem., September 6, 2002; 277(37): 34618 - 34625.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. M. Hennige, R. Lammers, W. Hoppner, D. Arlt, V. Strack, R. Teichmann, F. Machicao, A. Ullrich, H.-U. Haring, and M. Kellerer
Inhibition of Ret Oncogene Activity by the Protein Tyrosine Phosphatase SHP1
Endocrinology, October 1, 2001; 142(10): 4441 - 4447.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
E. de Graaff, S. Srinivas, C. Kilkenny, V. D'Agati, B. S. Mankoo, F. Costantini, and V. Pachnis
Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis
Genes & Dev., September 15, 2001; 15(18): 2433 - 2444.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. D. Ringel, N. Hayre, J. Saito, B. Saunier, F. Schuppert, H. Burch, V. Bernet, K. D. Burman, L. D. Kohn, and M. Saji
Overexpression and Overactivation of Akt in Thyroid Carcinoma
Cancer Res., August 1, 2001; 61(16): 6105 - 6111.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. M. Melillo, M. Santoro, S.-H. Ong, M. Billaud, A. Fusco, Y. R. Hadari, J. Schlessinger, and I. Lax
Docking Protein FRS2 Links the Protein Tyrosine Kinase RET and Its Oncogenic Forms with the Mitogen-Activated Protein Kinase Signaling Cascade
Mol. Cell. Biol., July 1, 2001; 21(13): 4177 - 4187.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Meng, D. G. de Rooij, K. Westerdahl, M. Saarma, and H. Sariola
Promotion of Seminomatous Tumors by Targeted Overexpression of Glial Cell Line-derived Neurotrophic Factor in Mouse Testis
Cancer Res., April 1, 2001; 61(8): 3267 - 3271.
[Abstract] [Full Text]

Home page
 NeoReviewsHome page
C. H. Contag, R. Weissleder, M. H. Bachmann, and S. E. Fraser
Applications of In Vivo Molecular Imaging in Biology and Medicine
NeoReviews, December 1, 2000; 1(12): e233 - 240.
[Full Text]

Home page
 J. Biol. Chem.Home page
B. Mograbi, R. Bocciardi, I. Bourget, R. Busca, N. Rochet, D. Farahi-Far, T. Juhel, and B. Rossi
Glial Cell Line-derived Neurotrophic Factor-stimulated Phosphatidylinositol 3-Kinase and Akt Activities Exert Opposing Effects on the ERK Pathway. IMPORTANCE FOR THE RESCUE OF NEUROECTODERMIC CELLS
J. Biol. Chem., November 21, 2001; 276(48): 45307 - 45319.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2000 by the American Association for Cancer Research.