Structural features and expression of an alternatively spliced growth factor type I receptor for follitropin signaling in the developing ovary.
The pleiotropic actions of pituitary follitropin (FSH), regulate the expression of many cell cycle genes controlling ovarian follicular development and differentiation. In this study we asked the question whether different receptor motifs are created by the alternative splicing of the single large 80-100 Kb receptor gene. A 1.2 Kb transcript identified from a cDNA library of hormone primed (immature) sheep ovaries, codes for a putative protein lacking the seven transmembrane segment. The receptor of 259 amino acids designated FSH-R3 is derived from a transcript comprising the first eight exons of the Gs coupled larger FSH receptor (R1) spliced to another DNA segment. This event produces a different carboxyl terminus at the junction creating a novel receptor motif with a single membrane spanning domain, assigning it to the growth factor type I receptor family. In transfected cells the expressed receptor localizes on the cell surface and specific antibodies directed against the unique C-terminal portion (residues 242-259) of FSH-R3 demonstrate the presence of the receptor protein in solubilized ovarian and testicular membrane preparations. FSH binding to the transfected cells induced [Ca2+]i identifying coupling of the R3 receptor to calcium signaling pathways. Thus, a growth factor type I receptor for FSH may be implicated in the growth promoting actions of FSH in the ovary. This is the first documentation of alternative splicing of a G protein coupled receptor gene creating a different signaling motif for cellular signaling.
Babu
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PS
Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Jiang
L
L
Sairam
A M
AM
Touyz
R M
RM
Sairam
M R
MR
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D020013:Calcium Signaling; D005260:Female; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D007106:Immune Sera; D008969:Molecular Sequence Data; D010053:Ovary / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011962:Receptors, FSH / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012756:Sheep
C412742:FSH-R3 protein, Ovis aries; D007106:Immune Sera; D011962:Receptors, FSH; D017978:Receptors, Growth Factor; D011986:Receptors, Somatotropin; D005640:Follicle Stimulating Hormone