| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Endocrinology, Vol 10, 367-379, Copyright © 1996 by Endocrine Society
ARTICLES |
SA Willis, CM Zimmerman, LI Li and LS Mathews
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109-0606, USA.
Activin is a protein growth and differentiation factor that initiates intracellular events through the activation of a complex of transmembrane protein serine kinases. Two subfamilies of receptor serine kinases, type I and type II, have been identified, and both receptor types may be required to generate a transmembrane signal. Investigation of the interaction between various activin receptors (ActRs) revealed that ActRs I and II could exist in a stable complex and that formation of that complex between transiently overexpressed molecules was not regulated by ligand. Analysis of phosphorylation suggested that activin induced phosphorylation of receptor I, probably at residues within a conserved glycine and serine-rich sequence in the juxtamembrane region referred to as the GS domain. Phosphorylation of the GS domain was dependent upon a functional ActRII. Introduction of an activin type I receptor, ALK4, into the mink lung epithelial cell line, L17, conferred activin responsiveness on those cells. Mutation of specific combinations of serines and threonines in the core sequence of the ALK4 GS domain to alanine rendered that receptor incompetent for signaling. Mutation of the same sets of residues to glutamic acid produced molecules that supported activin signaling but that did not display elevated basal signaling anticipated for a constitutively active receptor. However, mutation of a threonine residue in the carboxy-terminal half of the GS domain, T206, to glutamic acid yielded receptors with constitutive activity. Taken together, these results support a role for phosphorylation of type I ActRs in the generation of a biological signal.
This article has been cited by other articles:
 |
|
 |
|
  M. Murakami, H. Kawachi, K. Ogawa, Y. Nishino, and M. Funaba Receptor expression modulates the specificity of transforming growth factor-beta signaling pathways. Genes Cells, April 1, 2009; 14(4): 469 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Yamaguchi, A Kurisaki, N Yamakawa, K Minakuchi, and H Sugino FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type I receptor. J. Mol. Endocrinol., June 1, 2006; 36(3): 569 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nudi, J.-F. Ouimette, and J. Drouin Bone Morphogenic Protein (Smad)-Mediated Repression of Proopiomelanocortin Transcription by Interference with Pitx/Tpit Activity Mol. Endocrinol., May 1, 2005; 19(5): 1329 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lacerte, E.-H. Lee, R. Reynaud, L. Canaff, C. de Guise, D. Devost, S. Ali, G. N. Hendy, and J.-J. Lebrun Activin Inhibits Pituitary Prolactin Expression and Cell Growth through Smads, Pit-1 and Menin Mol. Endocrinol., June 1, 2004; 18(6): 1558 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Funaba, T. Ikeda, M. Murakami, K. Ogawa, K. Tsuchida, H. Sugino, and M. Abe Transcriptional Activation of Mouse Mast Cell Protease-7 by Activin and Transforming Growth Factor-{beta} Is Inhibited by Microphthalmia-associated Transcription Factor J. Biol. Chem., December 26, 2003; 278(52): 52032 - 52041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Bernard, K. H. Burns, B. Haupt, M. M. Matzuk, and T. K. Woodruff Normal Reproductive Function in InhBP/p120-Deficient Mice Mol. Cell. Biol., July 15, 2003; 23(14): 4882 - 4891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Mukasa, M. Nomura, T. Tanaka, K. Tanaka, Y. Nishi, T. Okabe, K. Goto, T. Yanase, and H. Nawata Activin Signaling through Type IB Activin Receptor Stimulates Aromatase Activity in the Ovarian Granulosa Cell-Like Human Granulosa (KGN) Cells Endocrinology, April 1, 2003; 144(4): 1603 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Funaba, C. M. Zimmerman, and L. S. Mathews Modulation of Smad2-mediated Signaling by Extracellular Signal-regulated Kinase J. Biol. Chem., October 25, 2002; 277(44): 41361 - 41368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Y. Qin, S. S. Lam, J. J. Correia, and K. Lin Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control Genes & Dev., August 1, 2002; 16(15): 1950 - 1963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsuzaki, S. Hanai, H. Kishi, Z. Liu, Y. Bao, A. Kikuchi, K. Tsuchida, and H. Sugino Regulation of Endocytosis of Activin Type II Receptors by a Novel PDZ Protein through Ral/Ral-binding Protein 1-dependent Pathway J. Biol. Chem., May 17, 2002; 277(21): 19008 - 19018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-G. Chen, H. M. Lui, S.-L. Lin, J. M. Lee, and S.-Y. Ying Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis by Activin Experimental Biology and Medicine, February 1, 2002; 227(2): 75 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Chapman and T. K. Woodruff Modulation of Activin Signal Transduction by Inhibin B and Inhibin-Binding Protein (InhBP) Mol. Endocrinol., April 1, 2001; 15(4): 668 - 679. [Abstract] [Full Text]
|
|
|
|
|
|
S. Miura, T. Takeshita, H. Asao, Y. Kimura, K. Murata, Y. Sasaki, J.-I. Hanai, H. Beppu, T. Tsukazaki, J. L. Wrana, et al. Hgs (Hrs), a FYVE Domain Protein, Is Involved in Smad Signaling through Cooperation with SARA Mol. Cell. Biol., December 15, 2000; 20(24): 9346 - 9355. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Zhou, H. Sun, D. C. Danila, S. R. Johnson, D. P. Sigai, X. Zhang, and A. Klibanski Truncated Activin Type I Receptor Alk4 Isoforms Are Dominant Negative Receptors Inhibiting Activin Signaling Mol. Endocrinol., December 1, 2000; 14(12): 2066 - 2075. [Abstract] [Full Text]
|
|
|
|
|
|
M. Funaba and L. S. Mathews Identification and Characterization of Constitutively Active Smad2 Mutants: Evaluation of Formation of Smad Complex and Subcellular Distribution Mol. Endocrinol., October 1, 2000; 14(10): 1583 - 1591. [Abstract] [Full Text]
|
|
|
|
|
|
W. Chen, T. K. Woodruff, and K. E. Mayo Activin A-Induced HepG2 Liver Cell Apoptosis: Involvement of Activin Receptors and Smad Proteins Endocrinology, March 1, 2000; 141(3): 1263 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shoji, K. Tsuchida, H. Kishi, N. Yamakawa, T. Matsuzaki, Z. Liu, T. Nakamura, and H. Sugino Identification and Characterization of a PDZ Protein That Interacts with Activin Type II Receptors J. Biol. Chem., February 25, 2000; 275(8): 5485 - 5492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wu, Y. Chen, B. Ozdamar, C. A. Gyuricza, P. A. Chong, J. L. Wrana, J. Massagué, and Y. Shi Structural Basis of Smad2 Recognition by the Smad Anchor for Receptor Activation Science, January 7, 2000; 287(5450): 92 - 97. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. H. D’Abronzo, B. Swearingen, A. Klibanski, and J. M. Alexander Mutational Analysis of Activin/Transforming Growth Factor-{beta} Type I and Type II Receptor Kinases in Human Pituitary Tumors J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1716 - 1721. [Abstract] [Full Text]
|
|
|
|
|
|
A. Lux, L. Attisano, and D. A. Marchuk Assignment of Transforming Growth Factor beta 1 and beta 3 and a Third New Ligand to the Type I Receptor ALK-1 J. Biol. Chem., April 9, 1999; 274(15): 9984 - 9992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ishisaki, K. Yamato, A. Nakao, K. Nonaka, M. Ohguchi, P. ten Dijke, and T. Nishihara Smad7 Is an Activin-inducible Inhibitor of Activin-induced Growth Arrest and Apoptosis in Mouse B Cells J. Biol. Chem., September 18, 1998; 273(38): 24293 - 24296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Di Simone, H. A. Hall, C. Welt, and A. L. Schneyer Activin Regulates {beta}A-Subunit and Activin Receptor Messenger Ribonucleic Acid and Cellular Proliferation in Activin-Responsive Testicular Tumor Cells Endocrinology, March 1, 1998; 139(3): 1147 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Zimmerman, M. S. T. Kariapper, and L. S. Mathews Smad Proteins Physically Interact with Calmodulin J. Biol. Chem., January 9, 1998; 273(2): 677 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Draper, M. M. Matzuk, V. J. Roberts, E. Cox, J. Weiss, J. P. Mather, and T. K. Woodruff Identification of an Inhibin Receptor in Gonadal Tumors from Inhibin alpha -Subunit Knockout Mice J. Biol. Chem., January 2, 1998; 273(1): 398 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Persson, S. Souchelnytskyi, P. Franzen, K. Miyazono, P. ten Dijke, and C.-H. Heldin Transforming Growth Factor (TGF-beta )-specific Signaling by Chimeric TGF-beta Type II Receptor with Intracellular Domain of Activin Type IIB Receptor J. Biol. Chem., August 22, 1997; 272(34): 21187 - 21194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-F. Ethier, J. G. Lussier, and D. W. Silversides Bovine Activin Receptor Type IIB Messenger Ribonucleic Acid Displays Alternative Splicing Involving a Sequence Homologous to Src-Homology 3 domain Binding Sites Endocrinology, June 1, 1997; 138(6): 2425 - 2434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Chang, P. Wilson, L. Mathews, and A Hemmati-Brivanlou A Xenopus type I activin receptor mediates mesodermal but not neural specification during embryogenesis Development, January 2, 1997; 124(4): 827 - 837. [Abstract] [PDF]
|
|
|
|
|
|
A. Osman, E. G. Niles, and P. T. LoVerde Identification and Characterization of a Smad2 Homologue from Schistosoma mansoni, a Transforming Growth Factor-beta Signal Transducer J. Biol. Chem., March 23, 2001; 276(13): 10072 - 10082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cocolakis, S. Lemay, S. Ali, and J.-J. Lebrun The p38 MAPK Pathway Is Required for Cell Growth Inhibition of Human Breast Cancer Cells in Response to Activin J. Biol. Chem., May 18, 2001; 276(21): 18430 - 18436. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
