Fig. 1.

Initial steps of PR activation. Progestins bind to cytoplasmic PR/ER complexes, anchored in the cell membrane by palmitoyl residues, and activate the Src/Ras/Erk pathway, leading to nuclear accumulation of activated pErk. The majority of PR is nuclear and associated with chaperones (Hsps). Upon binding of progestins, PR homodimers dissociate from chaperones, and a fraction of PR is phosphorylated by pErk, which also phosphorylates Msk1. A “PR-activated complex” composed of pPR/pErk/pMsk1 is formed. Progesterone induction also activates other kinase signaling pathways as Janus kinase (JAK)/Stat, phosphatidylinositol kinase (PI3K)/serine-threonine kinase (Akt), and Cdk2 (red asterisk).