TY - JOUR
T1 - Activated Gq-α potentiates platelet-derived growth factor-stimulated mitogenesis in confluent cell cultures
AU - De Vivo, Michael
AU - Iyengar, Ravi
PY - 1994/8/5
Y1 - 1994/8/5
N2 - We studied the effects of activation of the Gq-α signaling pathway on mitogenesis by expressing a mutant (Q209L), activated -subunit of Gq (αq*) in NIH-3T3 cells. A clonal NIH-3T3 cell line expressing αq* in an inducible manner was isolated. Expression of αq* is induced with dexamethasone, allowing the use of non-induced cells as controls for the effects of αq* expression. We found that, by itself, expression of αq* did not increase either DNA synthesis or mitogen-activated protein (MAP) kinase activity in serum-starved cells. Because αq* transforms cells grown in the presence of serum (De Vivo M., Chen, J., Codina, J., and Iyengar, R. (1992) J. Biol. Chem. 267, 18263-18266), we tested whether growth factor-stimulated signaling and mitogenesis were affected by expression of αq*. Platelet-derived growth factor (PDGF) stimulated thymidine incorporation modestly (50%) in contact-inhibited, confluent cell cultures. In cells expressing αq*, PDGF stimulated DNA synthesis up to 3-fold over basal. Concomitant with the potentiation of PDGF-stimulated DNA synthesis, expression of αq* potentiated PDGF-stimulated p44 MAP kinase activity. PDGF was much more effective in stimulating both DNA synthesis and p44 MAP kinase activity in subconfluent cell cultures and expression of αq* exerted little or no effect on PDGF-stimulated effects in subconfluent cells. These data show that cooperation between signaling pathways may occur in a cell state-specific fashion. Such cooperation in part may be responsible for the triggering of complex cellular responses such as cell transformation.
AB - We studied the effects of activation of the Gq-α signaling pathway on mitogenesis by expressing a mutant (Q209L), activated -subunit of Gq (αq*) in NIH-3T3 cells. A clonal NIH-3T3 cell line expressing αq* in an inducible manner was isolated. Expression of αq* is induced with dexamethasone, allowing the use of non-induced cells as controls for the effects of αq* expression. We found that, by itself, expression of αq* did not increase either DNA synthesis or mitogen-activated protein (MAP) kinase activity in serum-starved cells. Because αq* transforms cells grown in the presence of serum (De Vivo M., Chen, J., Codina, J., and Iyengar, R. (1992) J. Biol. Chem. 267, 18263-18266), we tested whether growth factor-stimulated signaling and mitogenesis were affected by expression of αq*. Platelet-derived growth factor (PDGF) stimulated thymidine incorporation modestly (50%) in contact-inhibited, confluent cell cultures. In cells expressing αq*, PDGF stimulated DNA synthesis up to 3-fold over basal. Concomitant with the potentiation of PDGF-stimulated DNA synthesis, expression of αq* potentiated PDGF-stimulated p44 MAP kinase activity. PDGF was much more effective in stimulating both DNA synthesis and p44 MAP kinase activity in subconfluent cell cultures and expression of αq* exerted little or no effect on PDGF-stimulated effects in subconfluent cells. These data show that cooperation between signaling pathways may occur in a cell state-specific fashion. Such cooperation in part may be responsible for the triggering of complex cellular responses such as cell transformation.
UR - http://www.scopus.com/inward/record.url?scp=0028170580&partnerID=8YFLogxK
M3 - Article
C2 - 8051041
AN - SCOPUS:0028170580
SN - 0021-9258
VL - 269
SP - 19671
EP - 19674
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 31
ER -