Inhibition of PI3-K or the Syk protein tyrosine kinase within NK cells prevents ERK activation following FcR and IL-12 stimulation. NK cells were pretreated overnight with 25 μM picetannol (Syk inhibitor) or wortmannin (PI3-K inhibitor) and then activated via FcγRIIIa cross-linking in the presence of 10 ng/mL IL-12 for 5 minutes at 37°C. Whole-cell lysates were probed for levels of p-ERK and total ERK, as indicated. Numbers below immunoblots represent the fold increase in phosphoprotein levels for each condition, normalized to total ERK and expressed in relative densitometric units. All results are representative of n = 5 healthy donors.