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Progressive cytoplasmic tail truncations of the lutropin-choriogonadotropin receptor prevent agonist- or phorbol ester-induced phosphorylation, impair agonist- or phorbol ester-induced desensitization, and enhance agonist-induced receptor down-regulation. 1996

Z Wang, and R W Hipkin, and M Ascoli
Department of Pharmacology, University of Iowa, College of Medicine Iowa City 52242-1109, USA.

Stably transfected human kidney 293 cells expressing the wild type rat LH/CG receptor (rLHR) or receptors with C-terminal tails truncated at residues 653, 631, or 628 (designated rLHR-t653, rLHR-t631, and rLHR-t628) were used to probe the importance of this region on the regulation of hormonal responsiveness. The chosen cells line express comparable densities of cell surface rLHR, bind human CG (hCG) with high affinity, and respond to hCG with increases in cAMP and inositol phosphate accumulation. Cells expressing rLHR-wt or rLHR-t653 responded to hCG, or phorbol 12-myristate-13-acetate (PMA) stimulation with a similar increase in rLHR phosphorylation. Neither of these two stimuli increased rLHR phosphorylation in cells expressing rLHR-t631 or rLHR-t628, however. The cell line expressing rLHR-t653, the phosphorylation-positive receptor mutant, desensitized normally in response to PMA or hCG stimulation. This truncated form of rLHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing rLHR-t631 or rLHR-t628, the two phosphorylation-negative receptor mutants, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the rLHR are involved in PMA-induced desensitization, hCG-induced de-sensitization, and hCG-induced down-regulation. These results also establish a positive correlation between rLHR phosphorylation and desensitization and a negative correlation between rLHR phosphorylation and down-regulation.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010703 Phorbol Esters Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. Phorbol Diester,Phorbol Ester,Phorbol Diesters,Diester, Phorbol,Diesters, Phorbol,Ester, Phorbol,Esters, Phorbol
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011974 Receptors, LH Those protein complexes or molecular sites on the surfaces and cytoplasm of gonadal cells that bind luteinizing or chorionic gonadotropic hormones and thereby cause the gonadal cells to synthesize and secrete sex steroids. The hormone-receptor complex is internalized from the plasma membrane and initiates steroid synthesis. Chorionic Gonadotropin Receptors,Human Chorionic Gonadotropin Receptors,ICSH Receptors,LH Receptors,LH-hCG Receptor,LH-hCG Receptors,Luteinizing Hormone Receptors,Lutropin Receptor,Lutropin Receptors,Receptors, Chorionic Gonadotropin,Receptors, Human Chorionic Gonadotropin,Receptors, Interstitial Cell-Stimulating Hormone,Receptors, Luteinizing Hormone,hCG Receptors,Chorionic Gonadotropin Receptor,Human Chorionic Gonadotropin Receptor,LH Receptor,Luteinizing Hormone Receptor,Receptors, ICSH,Receptors, Interstitial Cell Stimulating Hormone,Receptors, LH-hCG,Receptors, Lutropin,Receptors, hCG,hCG Receptor,Gonadotropin Receptor, Chorionic,Gonadotropin Receptors, Chorionic,Hormone Receptor, Luteinizing,Hormone Receptors, Luteinizing,LH hCG Receptor,LH hCG Receptors,Receptor, Chorionic Gonadotropin,Receptor, LH,Receptor, LH-hCG,Receptor, Luteinizing Hormone,Receptor, Lutropin,Receptor, hCG,Receptors, LH hCG
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D003593 Cytoplasm The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990) Protoplasm,Cytoplasms,Protoplasms
D006063 Chorionic Gonadotropin A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN). Chorionic Gonadotropin, Human,HCG (Human Chorionic Gonadotropin),Biogonadil,Choriogonadotropin,Choriogonin,Chorulon,Gonabion,Human Chorionic Gonadotropin,Pregnyl,Gonadotropin, Chorionic,Gonadotropin, Human Chorionic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic

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