| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242
Address all correspondence and requests for reprints to: Dr. Mario Ascoli, Department of Pharmacology, 2-319B BSB, 51 Newton Road, University of Iowa, Iowa City, Iowa 52242-1109. E-mail: mario-ascoli{at}uiowa.edu.
Using a Leydig tumor cell line (MA-10) transiently transfected with the human lutropin receptor (hLHR) and mutants thereof, we examined the identity of the G proteins activated by the agonist-engaged hLHR-wild type (wt) and by three of its naturally occurring constitutively active mutants. Two of the mutants examined, L457R in transmembrane helix 3 and D578Y in transmembrane helix 6, are germ-line mutations found in boys with Leydig cell hyperplasia and precocious puberty. The third, D578H, is a somatic mutation found in Leydig cell tumors in boys with precocious puberty. We show that the hLHR-wt and the three mutants activate the Gs, Gi/o, and Gq/11, but not the G12/13, families of G proteins. The activation of these G proteins by the hLHR-wt occurs only when engaged by agonist, but their activation by the L457R, D578Y, and D578H mutants occurs independently of agonist stimulation. We conclude that the G proteins activated by constitutively active mutants of the hLHR associated with Leydig cell hyperplasia or tumors are identical and are the same as those activated by the agonist-engaged hLHR-wt. If there was preferential activation of some G protein families by the somatic D578H mutation found in Leydig cell tumors as opposed to the germ line mutations found in Leydig cell hyperplasia, then one could envision mechanisms by which the D578H mutant would be oncogenic. The data presented here suggest that such mechanisms do not need to be considered.
This article has been cited by other articles:
 |
|
 |
|
  M. Zhang, Y.-X. Tao, G. L. Ryan, X. Feng, F. Fanelli, and D. L. Segaloff Intrinsic Differences in the Response of the Human Lutropin Receptor Versus the Human Follitropin Receptor to Activating Mutations J. Biol. Chem., August 31, 2007; 282(35): 25527 - 25539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Galet and M. Ascoli A Constitutively Active Mutant of the Human Lutropin Receptor (hLHR-L457R) Escapes Lysosomal Targeting and Degradation Mol. Endocrinol., November 1, 2006; 20(11): 2931 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shiraishi and M. Ascoli Activation of the Lutropin/Choriogonadotropin Receptor in MA-10 Cells Stimulates Tyrosine Kinase Cascades that Activate Ras and the Extracellular Signal Regulated Kinases (ERK1/2) Endocrinology, July 1, 2006; 147(7): 3419 - 3427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mizutani, K. Shiraishi, T. Welsh, and M. Ascoli Activation of the Lutropin/Choriogonadotropin Receptor in MA-10 Cells Leads to the Tyrosine Phosphorylation of the Focal Adhesion Kinase by a Pathway that Involves Src Family Kinases Mol. Endocrinol., March 1, 2006; 20(3): 619 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R S Bhaskaran and M Ascoli The post-endocytotic fate of the gonadotropin receptors is an important determinant of the desensitization of gonadotropin responses J. Mol. Endocrinol., April 1, 2005; 34(2): 447 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hirakawa and M. Ascoli The Lutropin/Choriogonadotropin Receptor-Induced Phosphorylation of the Extracellular Signal-Regulated Kinases in Leydig Cells Is Mediated by a Protein Kinase A-Dependent Activation of Ras Mol. Endocrinol., November 1, 2003; 17(11): 2189 - 2200. [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 |
