Fig. 2.

iRhom2 is required for the stimulated shedding of HB-EGF and KitL2 in response to physiological stimuli but not of TGFα. (A–F) WT and iRhom2^−/− mEFs were transfected with the AP-tagged ADAM17 substrates HB-EGF (A and B), KitL2 (C and D), or TGFα (E and F) and then activated with different stimuli for 30 min, as indicated [LPA (10 µM), PDGF (50 ng/mL), Thr (2 units/mL), or TNFα (10 ng/mL)]. All stimuli tested here activated ADAM17-mediated shedding, as evidenced by the significantly increased cleavage of HB-EGF (A), KitL2 (C), or TGFα (E) in WT mEFs. Identical experiments were performed with iRhom2^−/− mEFs, in which stimulation for 30 min with LPA, Thr, PDGF, or TNFα did not increase the shedding of HB-EGF (B) or KitL2 (D) but activated the release of TGFα (F). *P ≤ 0.05; ±SEM (n = 3 for A–F). ctrl, control.