Figure 2. CAR shedding is stimulated by the calcium ionophore ionomycin and the phorbol ester PMA.
(A) U87 CAR cells were treated with the calcium ionophore ionomycin at the indicated concentrations for 30 minutes. Ionomycin treatment stimulated the ECD shedding of CAR. (B) PMA treatment (25 ng/ml) of U87 CAR cells did not trigger CAR ECD shedding within one hour. At this concentration, 4 hours of PMA treatment led to robust CAR ECD shedding, but remained lower than constitutive shedding over 16 hours. Volumes of conditioned media loaded on SDS-PAGE were adjusted according to lysate protein concentrations. (C) The protein kinase C (PKC) inhibitor Gö 6983 decreased PMA-stimulated shedding of CAR ECD into conditioned media in a dose-dependent manner. PMA was used at a final concentration of 1 μM, and Gö 6983 at the following concentrations: + = 1 nM; ++ = 10 nM, and +++ = 100 nM. For the Western blots shown in these panels, the anti-CAR N-terminus antibodies 2239 or 2240 were used.