HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O'Neill, T. J. Articles by Gustafson, T. A. Search for Related Content PubMed PubMed Citation Articles by O'Neill, T. J. Articles by Gustafson, T. A. Social Bookmarking                      What's this?

Volume 272, Number 15, Issue of April 11, 1997 pp. 10035-10040
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Interaction of MAD2 with the Carboxyl Terminus of the Insulin Receptor but Not with the IGFIR
EVIDENCE FOR RELEASE FROM THE INSULIN RECEPTOR AFTER ACTIVATION

(Received for publication, December 31, 1996, and in revised form, February 4, 1997)

Thomas J. O'Neill , Youyan Zhu and Thomas A. Gustafson

From the Department of Physiology and the  Program in Molecular and Cellular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201

We have utilized the yeast two-hybrid system to identify proteins that interact with the cytoplasmic domain of the insulin receptor (IR). We identified a human cDNA encoding a protein that appears to be the human homolog of the yeast MAD2 protein, which we term hMAD2. The yeast MAD2 protein was first identified in a genetic screen to identify cell cycle checkpoint regulatory proteins, yet the mechanism by which MAD2 functions in cell cycle control is currently unclear. Here we show that hMAD2 requires the COOH-terminal 30 amino acids of the IR for interaction and that hMAD2 does not interact with the related insulin-like growth factor I receptor. Interestingly, hMAD2 does not require IR tyrosine autophosphorylation for interaction because it interacts with a kinase-dead IR in the yeast two-hybrid system. In support of this finding, hMAD2-GST fusions were found to interact strongly in vitro with receptors derived from noninsulin-stimulated cells. Furthermore, using two independent in vitro assays, IR activation was found to significantly reduce the interaction of hMAD2 with the IR. Lastly, we show that hMAD2 can be coimmunoprecipitated with the IR from Chinese hamster ovary IR cell lysates, suggesting that this interaction occurs in vivo in cells of mammalian origin. Our results suggest that hMAD2 represents a novel class of proteins that is specific for interaction with the IR as compared with the insulin-like growth factor I receptor and that interacts best with the inactive IR and is released upon receptor autophosphorylation. The function of hMAD2 and its potential role in insulin signaling remain to be elucidated.

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

This article has been cited by other articles:

				S. Ito, C. R. Mantel, M.-K. Han, S. Basu, S. Fukuda, S. Cooper, and H. E. Broxmeyer Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e cells Blood, March 1, 2007; 109(5): 1923 - 1930. [Abstract] [Full Text] [PDF]

				D. Pati, B. R. Haddad, A. Haegele, H. Thompson, F. S. Kittrell, A. Shepard, C. Montagna, N. Zhang, G. Ge, S. K. Otta, et al. Hormone-Induced Chromosomal Instability in p53-Null Mammary Epithelium Cancer Res., August 15, 2004; 64(16): 5608 - 5616. [Abstract] [Full Text] [PDF]

				J. Kaput, K. G. Klein, E. J. Reyes, W. A. Kibbe, C. A. Cooney, B. Jovanovic, W. J. Visek, and G. L. Wolff Identification of genes contributing to the obese yellow Avy phenotype: caloric restriction, genotype, diet x genotype interactions Physiol Genomics, August 11, 2004; 18(3): 316 - 324. [Abstract] [Full Text] [PDF]

				Y. Iwanaga, T. Kasai, K. Kibler, and K.-T. Jeang Characterization of Regions in hsMAD1 Needed for Binding hsMAD2. A POLYMORPHIC CHANGE IN AN hsMAD1 LEUCINE ZIPPER AFFECTS MAD1-MAD2 INTERACTION AND SPINDLE CHECKPOINT FUNCTION J. Biol. Chem., August 16, 2002; 277(34): 31005 - 31013. [Abstract] [Full Text] [PDF]

				S. Grisendi, B. Chambraud, I. Gout, P. M. Comoglio, and T. Crepaldi Ligand-regulated Binding of FAP68 to the Hepatocyte Growth Factor Receptor J. Biol. Chem., November 30, 2001; 276(49): 46632 - 46638. [Abstract] [Full Text] [PDF]

				M. Takeda, N. Dohmae, K. Takio, K.-i. Arai, and S. Watanabe Cell Cycle-dependent Interaction of Mad2 with Conserved Box1/2 Region of Human Granulocyte-Macrophage Colony-stimulating Factor Receptor Common beta c J. Biol. Chem., November 2, 2001; 276(45): 41803 - 41809. [Abstract] [Full Text] [PDF]

				J. J. Kim, B.-C. Park, Y. Kido, and D. Accili Mitogenic and Metabolic Effects of Type I IGF Receptor Overexpression in Insulin Receptor-Deficient Hepatocytes Endocrinology, August 1, 2001; 142(8): 3354 - 3360. [Abstract] [Full Text] [PDF]

				Y.-C. Liu, J. Pan, C. Zhang, W. Fan, M. Collinge, J. R. Bender, and S. M. Weissman A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2 PNAS, April 13, 1999; 96(8): 4313 - 4318. [Abstract] [Full Text] [PDF]

				A. Kasus-Jacobi, D. Perdereau, C. Auzan, E. Clauser, E. Van Obberghen, F. Mauvais-Jarvis, J. Girard, and A.-F. Burnol Identification of the Rat Adapter Grb14 as an Inhibitor of Insulin Actions J. Biol. Chem., October 2, 1998; 273(40): 26026 - 26035. [Abstract] [Full Text] [PDF]

				G. Poelzl, Y. Kasai, N. Mochizuki, P. W. Shaul, M. Brown, and M. E. Mendelsohn Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2 PNAS, March 14, 2000; 97(6): 2836 - 2839. [Abstract] [Full Text] [PDF]