Mechanism of PKD catalytic activation in response to bombesin in Swiss
3T3 cells; differential regulation of Ser744 and Ser748
phosphorylation. A, inhibition of in vitro PKD catalytic
activity by K252a. Swiss 3T3 PKD.GFP cells were stimulated with bombesin for
10 min and then lysed in ice-cold buffer. PKD was immunoprecipitated from
lysates with an anti-PKD C-20 antibody bound to protein A-agarose and assayed
for syntide-2 phosphorylation activity in the presence of various
concentrations of K252a (as indicated) or 3.5 μm GF1.
B, Swiss 3T3-PKD.GFP were incubated in the absence (–) or in
the presence 3.5 μm GF1 or 1 μm K252a as indicated
for 1 h before stimulation with 10 nm bombesin for either 10 or 240
min. The cultures were then lysed with 2× SDS-PAGE sample buffer.
C, Swiss 3T3-PKD.GFP or Swiss 3T3-PKDK618N.GFP were incubated in the
absence (–) or in the presence (+) of 2.5 μm Gö 6983
for 1 h before stimulation of the cells with 10 nm bombesin for the
indicated times. The cultures were then lysed with 2× SDS-PAGE sample
buffer. All samples were analyzed by SDS-PAGE and immunoblotting with the
antibodies phospho PKD Ser(P)916, Ser(P)744,
Ser(P)748, and PKD-C20 to verify equal loading. The results shown
here are representative autoluminograms; similar results were obtained in four
independent experiments in panel B and three independent experiments
in panel C. D, recombinant purified PKD was incubated with 100
μm ATP in kinase buffer for the times indicated. The reactions
were terminated with 2× SDS-PAGE sample buffer. E, PKD eluted
from Swiss 3T3 immunocomplexes was incubated with 200 μm ATP in
kinase buffer for the times indicated. The reactions were terminated with
2× SDS-PAGE sample buffer. All samples were analyzed by SDS-PAGE and
immunoblotting with the following antibodies phospho-PKD Ser(P)744
and Ser(P)748. All other details are as described under
“Experimental Procedures.” The results shown here are
representative autoluminograms; similar results were obtained in two
independent experiments.