Sex hormone-binding globulin receptor signal transduction proceeds via a G protein.
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.
Department of Medicine, St. Luke's/Roosevelt Hospital Center and College of Physicians and Surgeons, Columbia University, New York, NY 10019, USA.
A M
AM
Nakhla
J
J
Leonard
D J
DJ
Hryb
W
W
Rosner
D000242:Cyclic AMP / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D011956:Receptors, Cell Surface; D012738:Sex Hormone-Binding Globulin; C063572:sex hormone-binding globulin receptor; D000242:Cyclic AMP; D019204:GTP-Binding Proteins