TY - JOUR
T1 - Calcium inhibits epidermal growth factor-induced activation of p21ras in human primary keratinocytes
AU - Medema, J. P.
AU - Sark, M. W.
AU - Backendorf, C.
AU - Bos, J. L.
PY - 1994
Y1 - 1994
N2 - Human primary keratinocytes are an elegant model system to study the balance between proliferation and differentiation. Both epidermal growth factor (EGF) and extracellular calcium have been implicated to function in the control of this balance, although the molecular mechanism underlying this process is poorly understood. In this study, we measured the effect of both EGF and calcium treatment on activation of p21ras and ERK2. We found that addition of EGF stimulated the activity of ERK2. This stimulation was dependent on p21ras activity, since it was completely abolished by expression of a dominant negative mutant of p21ras (p21ras(Asn-17)). Raising the level of extracellular calcium (1.8 mM) did not result in activation of ERK2. On the contrary, calcium treatment inhibited EGF-induced stimulation of ERK2 activity. In order to determine the site at which calcium treatment interferes in EGF-induced signaling, we analyzed the effect of calcium on the various steps that are involved in EGF-induced, p21ras-dependent activation of ERK2. We observed that calcium treatment inhibited EGF-induced p21ras activation. Calcium treatment, however, did not interfere with EGF-induced EGF receptor autophosphorylation or association of mammalian SOS with the EGF receptor and Shc. This, together with the observation that calcium treatment alone decreased the basal level of p21ras activity, indicates that calcium treatment interferes in EGF-mediated signaling at the level of p21ras. This type of cross talk may play a role in the decision between proliferation and differentiation in human primary keratinocytes
AB - Human primary keratinocytes are an elegant model system to study the balance between proliferation and differentiation. Both epidermal growth factor (EGF) and extracellular calcium have been implicated to function in the control of this balance, although the molecular mechanism underlying this process is poorly understood. In this study, we measured the effect of both EGF and calcium treatment on activation of p21ras and ERK2. We found that addition of EGF stimulated the activity of ERK2. This stimulation was dependent on p21ras activity, since it was completely abolished by expression of a dominant negative mutant of p21ras (p21ras(Asn-17)). Raising the level of extracellular calcium (1.8 mM) did not result in activation of ERK2. On the contrary, calcium treatment inhibited EGF-induced stimulation of ERK2 activity. In order to determine the site at which calcium treatment interferes in EGF-induced signaling, we analyzed the effect of calcium on the various steps that are involved in EGF-induced, p21ras-dependent activation of ERK2. We observed that calcium treatment inhibited EGF-induced p21ras activation. Calcium treatment, however, did not interfere with EGF-induced EGF receptor autophosphorylation or association of mammalian SOS with the EGF receptor and Shc. This, together with the observation that calcium treatment alone decreased the basal level of p21ras activity, indicates that calcium treatment interferes in EGF-mediated signaling at the level of p21ras. This type of cross talk may play a role in the decision between proliferation and differentiation in human primary keratinocytes
U2 - https://doi.org/10.1128/MCB.14.11.7078
DO - https://doi.org/10.1128/MCB.14.11.7078
M3 - Article
C2 - 7935423
SN - 0270-7306
VL - 14
SP - 7078
EP - 7085
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 11
ER -