|
Comment |
Nechamen CA, et al reported that Human Follicle-Stimulating Hormone (FSH) Receptor Interacts with the Adaptor Protein APPL1 in HEK 293 Cells: Potential Involvement of the PI3K Pathway in FSH Signaling.
Selection of a dominant follicle that will ovulate likely occurs by activation of cell survival pathways and suppression of death promoting pathways in a mechanism involving follicle stimulating hormone (FSH) and its cognate receptor (FSHR). A yeast two hybrid screen of an ovarian cDNA library was employed to identify potential interacting partners with human FSHR intracellular loops 1 and 2. Among eight cDNA clones identified in the screen, APPL1 [Adaptor protein containing PH domain, PTB domainand Leucine zipper motif] (also known as APPL or DIP13a) was chosen for further analysis. APPL1 appears to co-immunoprecipitate with FSHR in HEK293 cells stably expressing FSHR, confirming APPL1 as a potential FSHR interacting partner. The phosphorylation status of members of the phosphatidyl inositol-3-kinase (PI3K)/Akt signaling pathway was also examined due to the proposed role of APPL1 in the anti-apoptotic PI3K/Akt pathway. FOXO1a, also referred to as Forkhead Homologue in Rhabdomyosarcoma (FKHR), is a downstream effector in the pathway and tightly linked to expression of pro-apoptotic genes. FOXO1a, but not the upstream kinase Akt, is rapidly phosphorylated and FOXO1a is thereby inactivated when 293/FSHR cells are treated with FSH. In addition, FSHR co-immunoprecipitates with Akt. The identification of APPL1 as a potential interactor with FSHR and the finding that FOXO1a is phosphorylated in response to FSH provide a possible link between FSH and PI3K/Akt signaling, which may help to delineate a survival mechanism whereby FSH selects the dominant follicle to survive.
|