A potential role for extracellular signal-regulated kinases in prostaglandin F(2α)-induced protein synthesis in smooth muscle cells

Rao Gadiparthi, Nageswara R. Madamanchi, Manjiri Lele, Laxmisilpa Gadiparthi, Anne Claude Gingras, Thomas E. Eling, Nahum Sonenberg

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

To understand the mechanisms of prostaglandin F(2α) (PGF(2α))-induced protein synthesis in vascular smooth muscle cells (VSMC), we have studied its effect on two major signal transduction pathways: mitogen-activated protein kinases and phosphatidylinositol 3-kinase (PI3-kinase) and their downstream targets ribosomal protein S6 kinase (p70(S6k)) and eukaryotic initiation factor eIF4E and its regulator 4E-BP1. PGF(2α) induced the activities of extracellular signal-regulated kinase 2 (ERK2) and Jun N-terminal kinase 1 (JNK1) groups of mitogen-activated protein kinases, PI3-kinase, and p70(S6k) in a time-dependent manner in growth-arrested VSMC. PGF(2α) also induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and basic fibroblast growth factor-2 (bFGF-2) expression in VSMC. Whereas inhibition of PI3-kinase by wortmannin completely blocked the p70(S6k) activation, it only partially decreased the ERK2 activity, and had no significant effect on global protein synthesis and bFGF-2 expression induced by PGF(2α). Rapamycin, a potent inhibitor of p70(S6k), also failed to prevent PGF(2α)- induced global protein synthesis and bFGF-2 expression, although it partially decreased ERK2 activity. In contrast, inhibition of ERK2 activity by PD 098059 led to a significant loss of PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and bFGF-2 expression. PGF(2α)- induced phosphorylation of eIF4E and 4E-BP1 was also found to be sensitive to inhibition by both wortmannin and rapamycin. These findings demonstrate that 1) PI3-kinase-dependent and independent mechanisms appear to be involved in PGF(2α)-induced activation of ERK2; 2) PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation appear to be mediated by both ERK-dependent and PI3-kinase- dependent rapamycin-sensitive mechanisms; and 3) ERK-dependent eIF4E phosphorylation but not PI3-kinase-dependent p70(S6k) activation correlates with PGF(2α)-induced global protein synthesis and bFGF-2 expression in VSMC.

Original languageEnglish (US)
Pages (from-to)12925-12932
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number18
DOIs
StatePublished - Apr 30 1999
Externally publishedYes

Fingerprint

Extracellular Signal-Regulated MAP Kinases
Prostaglandins F
Fibroblast Growth Factor 2
Smooth Muscle Myocytes
Muscle
Phosphatidylinositol 3-Kinase
Cells
Phosphorylation
Mitogen-Activated Protein Kinase 1
70-kDa Ribosomal Protein S6 Kinases
Proteins
Vascular Smooth Muscle
Sirolimus
Chemical activation
Mitogen-Activated Protein Kinases
MAP Kinase Kinase 1
Ribosomal Protein S6 Kinases
Eukaryotic Initiation Factors
Signal transduction
Signal Transduction

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A potential role for extracellular signal-regulated kinases in prostaglandin F(2α)-induced protein synthesis in smooth muscle cells. / Gadiparthi, Rao; Madamanchi, Nageswara R.; Lele, Manjiri; Gadiparthi, Laxmisilpa; Gingras, Anne Claude; Eling, Thomas E.; Sonenberg, Nahum.

In: Journal of Biological Chemistry, Vol. 274, No. 18, 30.04.1999, p. 12925-12932.

Research output: Contribution to journalArticle

Gadiparthi, Rao ; Madamanchi, Nageswara R. ; Lele, Manjiri ; Gadiparthi, Laxmisilpa ; Gingras, Anne Claude ; Eling, Thomas E. ; Sonenberg, Nahum. / A potential role for extracellular signal-regulated kinases in prostaglandin F(2α)-induced protein synthesis in smooth muscle cells. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 18. pp. 12925-12932.
@article{5b00043324e641fa94d2e171804ad31b,
title = "A potential role for extracellular signal-regulated kinases in prostaglandin F(2α)-induced protein synthesis in smooth muscle cells",
abstract = "To understand the mechanisms of prostaglandin F(2α) (PGF(2α))-induced protein synthesis in vascular smooth muscle cells (VSMC), we have studied its effect on two major signal transduction pathways: mitogen-activated protein kinases and phosphatidylinositol 3-kinase (PI3-kinase) and their downstream targets ribosomal protein S6 kinase (p70(S6k)) and eukaryotic initiation factor eIF4E and its regulator 4E-BP1. PGF(2α) induced the activities of extracellular signal-regulated kinase 2 (ERK2) and Jun N-terminal kinase 1 (JNK1) groups of mitogen-activated protein kinases, PI3-kinase, and p70(S6k) in a time-dependent manner in growth-arrested VSMC. PGF(2α) also induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and basic fibroblast growth factor-2 (bFGF-2) expression in VSMC. Whereas inhibition of PI3-kinase by wortmannin completely blocked the p70(S6k) activation, it only partially decreased the ERK2 activity, and had no significant effect on global protein synthesis and bFGF-2 expression induced by PGF(2α). Rapamycin, a potent inhibitor of p70(S6k), also failed to prevent PGF(2α)- induced global protein synthesis and bFGF-2 expression, although it partially decreased ERK2 activity. In contrast, inhibition of ERK2 activity by PD 098059 led to a significant loss of PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and bFGF-2 expression. PGF(2α)- induced phosphorylation of eIF4E and 4E-BP1 was also found to be sensitive to inhibition by both wortmannin and rapamycin. These findings demonstrate that 1) PI3-kinase-dependent and independent mechanisms appear to be involved in PGF(2α)-induced activation of ERK2; 2) PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation appear to be mediated by both ERK-dependent and PI3-kinase- dependent rapamycin-sensitive mechanisms; and 3) ERK-dependent eIF4E phosphorylation but not PI3-kinase-dependent p70(S6k) activation correlates with PGF(2α)-induced global protein synthesis and bFGF-2 expression in VSMC.",
author = "Rao Gadiparthi and Madamanchi, {Nageswara R.} and Manjiri Lele and Laxmisilpa Gadiparthi and Gingras, {Anne Claude} and Eling, {Thomas E.} and Nahum Sonenberg",
year = "1999",
month = "4",
day = "30",
doi = "10.1074/jbc.274.18.12925",
language = "English (US)",
volume = "274",
pages = "12925--12932",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - A potential role for extracellular signal-regulated kinases in prostaglandin F(2α)-induced protein synthesis in smooth muscle cells

AU - Gadiparthi, Rao

AU - Madamanchi, Nageswara R.

AU - Lele, Manjiri

AU - Gadiparthi, Laxmisilpa

AU - Gingras, Anne Claude

AU - Eling, Thomas E.

AU - Sonenberg, Nahum

PY - 1999/4/30

Y1 - 1999/4/30

N2 - To understand the mechanisms of prostaglandin F(2α) (PGF(2α))-induced protein synthesis in vascular smooth muscle cells (VSMC), we have studied its effect on two major signal transduction pathways: mitogen-activated protein kinases and phosphatidylinositol 3-kinase (PI3-kinase) and their downstream targets ribosomal protein S6 kinase (p70(S6k)) and eukaryotic initiation factor eIF4E and its regulator 4E-BP1. PGF(2α) induced the activities of extracellular signal-regulated kinase 2 (ERK2) and Jun N-terminal kinase 1 (JNK1) groups of mitogen-activated protein kinases, PI3-kinase, and p70(S6k) in a time-dependent manner in growth-arrested VSMC. PGF(2α) also induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and basic fibroblast growth factor-2 (bFGF-2) expression in VSMC. Whereas inhibition of PI3-kinase by wortmannin completely blocked the p70(S6k) activation, it only partially decreased the ERK2 activity, and had no significant effect on global protein synthesis and bFGF-2 expression induced by PGF(2α). Rapamycin, a potent inhibitor of p70(S6k), also failed to prevent PGF(2α)- induced global protein synthesis and bFGF-2 expression, although it partially decreased ERK2 activity. In contrast, inhibition of ERK2 activity by PD 098059 led to a significant loss of PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and bFGF-2 expression. PGF(2α)- induced phosphorylation of eIF4E and 4E-BP1 was also found to be sensitive to inhibition by both wortmannin and rapamycin. These findings demonstrate that 1) PI3-kinase-dependent and independent mechanisms appear to be involved in PGF(2α)-induced activation of ERK2; 2) PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation appear to be mediated by both ERK-dependent and PI3-kinase- dependent rapamycin-sensitive mechanisms; and 3) ERK-dependent eIF4E phosphorylation but not PI3-kinase-dependent p70(S6k) activation correlates with PGF(2α)-induced global protein synthesis and bFGF-2 expression in VSMC.

AB - To understand the mechanisms of prostaglandin F(2α) (PGF(2α))-induced protein synthesis in vascular smooth muscle cells (VSMC), we have studied its effect on two major signal transduction pathways: mitogen-activated protein kinases and phosphatidylinositol 3-kinase (PI3-kinase) and their downstream targets ribosomal protein S6 kinase (p70(S6k)) and eukaryotic initiation factor eIF4E and its regulator 4E-BP1. PGF(2α) induced the activities of extracellular signal-regulated kinase 2 (ERK2) and Jun N-terminal kinase 1 (JNK1) groups of mitogen-activated protein kinases, PI3-kinase, and p70(S6k) in a time-dependent manner in growth-arrested VSMC. PGF(2α) also induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and basic fibroblast growth factor-2 (bFGF-2) expression in VSMC. Whereas inhibition of PI3-kinase by wortmannin completely blocked the p70(S6k) activation, it only partially decreased the ERK2 activity, and had no significant effect on global protein synthesis and bFGF-2 expression induced by PGF(2α). Rapamycin, a potent inhibitor of p70(S6k), also failed to prevent PGF(2α)- induced global protein synthesis and bFGF-2 expression, although it partially decreased ERK2 activity. In contrast, inhibition of ERK2 activity by PD 098059 led to a significant loss of PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation, global protein synthesis, and bFGF-2 expression. PGF(2α)- induced phosphorylation of eIF4E and 4E-BP1 was also found to be sensitive to inhibition by both wortmannin and rapamycin. These findings demonstrate that 1) PI3-kinase-dependent and independent mechanisms appear to be involved in PGF(2α)-induced activation of ERK2; 2) PGF(2α)-induced eIF4E and 4E-BP1 phosphorylation appear to be mediated by both ERK-dependent and PI3-kinase- dependent rapamycin-sensitive mechanisms; and 3) ERK-dependent eIF4E phosphorylation but not PI3-kinase-dependent p70(S6k) activation correlates with PGF(2α)-induced global protein synthesis and bFGF-2 expression in VSMC.

UR - http://www.scopus.com/inward/record.url?scp=0033617152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033617152&partnerID=8YFLogxK

U2 - 10.1074/jbc.274.18.12925

DO - 10.1074/jbc.274.18.12925

M3 - Article

VL - 274

SP - 12925

EP - 12932

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -