In PC Cl3 cells, a rat thyroid cell line, angiotensin (Ang 11) activates the atypical protein kinase C-zeta (PKC-zeta) and the extracellular signal-regulated kinase (ERK) pathways. We here studied the Ang It effects on PC C13 cell proliferation. It was found that Ang 11: (1) induced the phosphorylation of protein kinase B (PKB), (2) induced the growth-related early gene c-fos expression, (3) enhanced the cyclin E and p27(kip) expression, (4) had no effects on Cdk2, and (5) did not affect the transition from G0/G1 to S phase. Inhibition of phosphoinositide-3kinase by LY294002 further increased the effect of Ang 11 on p27(kip) induction, whilst PKCs inhibition by GF109203X decreased such effect. The role of PKC-zeta was recognized by the use of a synthetic myristoylated peptide with sequences based on the endogenous PKC-zeta pseuclosubstrate and by PKC-zeta downregulation using the small interfering RNA (siRNA). Insulin had a replicating effect on PC C13 cells, induced the phosphorylation of PKB, decreased p27(kip) expression and had no effect on the PKC-zeta cytosol-to-membrane translocation. PC C13 cell proliferation was induced more potently by simultaneous stimulation with insulin and Ang 11 than by stimulation with insulin alone, and the effect on p27(kip) expression was similar to that obtained with insulin only. These observations demonstrate that in PC Cl3 cells Ang 11 causes a block in G1 phase, although both ERK and PKB pathways are activated, and this effect may be due to the upregulation of p27(kip) and PKC- operativity.
Angiotensin II does not stimulate proliferation of rat thyroid PC Cl3 cell line
MUSCELLA, Antonella;STORELLI, Carlo;MARSIGLIANTE, Santo
Ultimo
2006-01-01
Abstract
In PC Cl3 cells, a rat thyroid cell line, angiotensin (Ang 11) activates the atypical protein kinase C-zeta (PKC-zeta) and the extracellular signal-regulated kinase (ERK) pathways. We here studied the Ang It effects on PC C13 cell proliferation. It was found that Ang 11: (1) induced the phosphorylation of protein kinase B (PKB), (2) induced the growth-related early gene c-fos expression, (3) enhanced the cyclin E and p27(kip) expression, (4) had no effects on Cdk2, and (5) did not affect the transition from G0/G1 to S phase. Inhibition of phosphoinositide-3kinase by LY294002 further increased the effect of Ang 11 on p27(kip) induction, whilst PKCs inhibition by GF109203X decreased such effect. The role of PKC-zeta was recognized by the use of a synthetic myristoylated peptide with sequences based on the endogenous PKC-zeta pseuclosubstrate and by PKC-zeta downregulation using the small interfering RNA (siRNA). Insulin had a replicating effect on PC C13 cells, induced the phosphorylation of PKB, decreased p27(kip) expression and had no effect on the PKC-zeta cytosol-to-membrane translocation. PC C13 cell proliferation was induced more potently by simultaneous stimulation with insulin and Ang 11 than by stimulation with insulin alone, and the effect on p27(kip) expression was similar to that obtained with insulin only. These observations demonstrate that in PC Cl3 cells Ang 11 causes a block in G1 phase, although both ERK and PKB pathways are activated, and this effect may be due to the upregulation of p27(kip) and PKC- operativity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
