TY - JOUR
T1 - Differential effects of lysosomotropic amines and polyamines on processing and biological activity of EGF
AU - Widelitz, Randall B.
AU - Matrisian, Lynn M.
AU - Russell, Diane H.
AU - Magun, Bruce E.
N1 - Funding Information:
The authors wish to acknowledge the technical assistance of Chris Fennie, Herb Wagner, Joel Finman, and Natalie Miller. This work was supportedb y NIH Grants CA29290,C A14783,C A00732 and NRSA training grant CA092 13.
PY - 1984/11
Y1 - 1984/11
N2 - The effects of lysosomotropic amines and polyamines on rat fibroblasts were studied after the administration of epidermal growth factor (EGF) in order to determine whether the intracellular processing of EGF was important for transmission of its biological signal. Following the addition of EGF, cell cultures exhibited a dose-dependent increase in ornithine decarboxylase (ODC) activity. This increase in ODC activity was drastically reduced by both methylamine, a representative lysosomotropic amine, and putrescine, a polyamine precursor. However, inasmuch as methylamine inhibited EGF-induced DNA synthesis by greater than 50%, putrescine had no inhibitory effect. Lysosomotropic amines, but not polyamines, prevented EGF processing as evidenced by their ability to block the release of intracellular 125EGF and by their ability to inhibit the formation of the final intracellular processed product of EGF, as determined by isoelectric focusing. These data suggest that the processing of EGF is consistent with the induction of DNA synthesis and ODC activity. The cellular mechanisms involved in inhibition of ODC induction by polyamines appear to be distinct from those involved in lysosomotropic amines.
AB - The effects of lysosomotropic amines and polyamines on rat fibroblasts were studied after the administration of epidermal growth factor (EGF) in order to determine whether the intracellular processing of EGF was important for transmission of its biological signal. Following the addition of EGF, cell cultures exhibited a dose-dependent increase in ornithine decarboxylase (ODC) activity. This increase in ODC activity was drastically reduced by both methylamine, a representative lysosomotropic amine, and putrescine, a polyamine precursor. However, inasmuch as methylamine inhibited EGF-induced DNA synthesis by greater than 50%, putrescine had no inhibitory effect. Lysosomotropic amines, but not polyamines, prevented EGF processing as evidenced by their ability to block the release of intracellular 125EGF and by their ability to inhibit the formation of the final intracellular processed product of EGF, as determined by isoelectric focusing. These data suggest that the processing of EGF is consistent with the induction of DNA synthesis and ODC activity. The cellular mechanisms involved in inhibition of ODC induction by polyamines appear to be distinct from those involved in lysosomotropic amines.
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U2 - 10.1016/0014-4827(84)90777-8
DO - 10.1016/0014-4827(84)90777-8
M3 - Article
C2 - 6333348
AN - SCOPUS:0021680677
SN - 0014-4827
VL - 155
SP - 163
EP - 170
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -