Signaling mechanisms for PGF2α and AL-8810 stimulation of FP receptor. PGF2α activates ERK1/2 through the canonical Gαq/11-PKC-dependent pathway, which seems to be mostly EGFR independent in HEK293 cells, and results in activated ERK1/2 remaining mainly in the cytosol at early time points and translocates to the nucleus at later time points. On the other hand, AL-8810 activates ERK1/2 through FP receptor-dependent EGFR transactivation, via Src kinase and EGF shedding, probably via matrix metalloproteases, leading to a rapid and transient activation of ERK1/2 in the nucleus. RTK, Receptor tyrosine kinase.