Figure 7.

RXFP4 receptor signal transduction pathways. Inhibitors used in studying RXFP4 receptor signalling mechanisms are boxed in red. Following INSL5 stimulation, RXFP4 receptors recruit multiple Gα_i/o subunits (predominantly Gα_oA, Gα_oB, Gα_i2) that activate a range of signalling pathways, including cAMP inhibition, ERK1/2 (Thr²⁰²/Tyr²⁰⁴), Akt (Thr³⁰⁸/Ser⁴⁷³) p38MAPK (Thr¹⁸⁰/Tyr¹⁸²) and S6RP (Ser²³⁵/²³⁶) via intermediary pathways such as mTORC1/C2, Src, PI3K and MEK1/2, leading to enhanced cell proliferation. Activated RXFP4 receptors interact with GRK2 and β‐arrestins (β‐Arr 1/2), which leads to movement of the receptor away from the plasma membrane into early endosome compartments. Note: speculative pathways are shown with dotted lines. mammalian target of rapamycin, mTOR; phosphoinositide‐dependent kinase, PDK.