| Autor: |
Nakhla AM; Department of Medicine, St. Luke's/Roosevelt Hospital Center and College of Physicians and Surgeons, Columbia University, New York, NY 10019, USA., Leonard J, Hryb DJ, Rosner W |
| Jazyk: |
angličtina |
| Zdroj: |
Steroids [Steroids] 1999 Mar; Vol. 64 (3), pp. 213-6. |
| DOI: |
10.1016/s0039-128x(98)00084-1 |
| Abstrakt: |
The plasma protein, sex hormone-binding globulin (SHBG) binds to a receptor (R(SHBG)) on cell membranes to form an SHBG-R(SHBG) complex. When an appropriate steroid binds to this complex, there is a rapid rise in intracellular cyclic adenosine monophosphate (cAMP). Although the system is moderately well characterized, the molecular cloning of R(SHBG) has not been accomplished and there is a paucity of evidence regarding the mechanism of transmission of the R(SHBG) signal. In this communication, we offer two independent lines of evidence that a G protein is involved in R(SHBG) signal propagation. Exposure of cell membranes containing R(SHBG) to a non-hydrolyzable analog of guanosine triphosphate (guanylyl-5'-imidodiphosphate) caused a substantive decrease in the binding of SHBG to R(SHBG). This behavior is typical of membrane receptors coupled to G proteins and has been used by others as evidence to support that relationship. Another set of experiments involved the assumption that, if R(SHBG)-induced increases in cAMP were diminished when the wild-type alpha subunit of a G protein was replaced with mutants that were inefficient/ineffective in signal transduction, then the idea that G proteins were involved in that signal would be buttressed. Hence, we infected COS-1 cells with a construct containing such mutants, along with a cAMP response element reporter, and demonstrated a marked decrease in R(SHBG)-engendered reporter activity, e.g. cAMP generation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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