The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors

Caroline R. Weinstein-Oppenheimer; William L. Blalock; Linda S. Steelman; Fumin Chang; James A. McCubrey

doi:10.1016/S0163-7258(00)00085-1

The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors

Caroline R. Weinstein-Oppenheimer, William L. Blalock, Linda S. Steelman, Fumin Chang, James A. McCubrey

Research output: Contribution to journal › Review article › peer-review

83 Scopus citations

Abstract

This review focuses on the Ras-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signal transduction pathway and the consequences of its unregulation in the development of cancer. The roles of some of the cell membrane receptors involved in the activation of this pathway, the G-protein Ras, the Raf, MEK and ERK kinases, the phosphatases that regulate these kinases, as well as the downstream transcription factors that become activated, are discussed. The roles of the Ras-Raf-MEK-ERK pathway in the regulation of apoptosis and cell cycle progression are also analyzed. In addition, potential targets for pharmacological intervention in growth factor-responsive cells are evaluated.

Original language	English (US)
Pages (from-to)	229-279
Number of pages	51
Journal	Pharmacology and Therapeutics
Volume	88
Issue number	3
DOIs	https://doi.org/10.1016/S0163-7258(00)00085-1
State	Published - 2000
Externally published	Yes

Keywords

ERK
Growth factors
MEK
Raf
Ras
Receptors

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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10.1016/S0163-7258(00)00085-1

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title = "The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors",

abstract = "This review focuses on the Ras-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signal transduction pathway and the consequences of its unregulation in the development of cancer. The roles of some of the cell membrane receptors involved in the activation of this pathway, the G-protein Ras, the Raf, MEK and ERK kinases, the phosphatases that regulate these kinases, as well as the downstream transcription factors that become activated, are discussed. The roles of the Ras-Raf-MEK-ERK pathway in the regulation of apoptosis and cell cycle progression are also analyzed. In addition, potential targets for pharmacological intervention in growth factor-responsive cells are evaluated.",

keywords = "ERK, Growth factors, MEK, Raf, Ras, Receptors",

author = "Weinstein-Oppenheimer, {Caroline R.} and Blalock, {William L.} and Steelman, {Linda S.} and Fumin Chang and McCubrey, {James A.}",

note = "Funding Information: We appreciate the artwork done by Ms. Catherine Spruill. We appreciate the helpful comments on this review by Dr. Joseph Cory. This work was supported in part by a grant (R01CA51025) from the National Cancer Institute and the North Carolina Biotechnology Center (9805-ARG-0006) to J.A.M. Caroline Weinstein-Oppenheimer was a recipient of a Fulbright-LASPAU scholarship, an International Peace scholarship from the Promotion of Education Organization, and an Organization of American States (OAS) scholarship.",

year = "2000",

doi = "10.1016/S0163-7258(00)00085-1",

language = "English (US)",

volume = "88",

pages = "229--279",

journal = "Pharmacology and Therapeutics",

issn = "0163-7258",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors

AU - Weinstein-Oppenheimer, Caroline R.

AU - Blalock, William L.

AU - Steelman, Linda S.

AU - Chang, Fumin

AU - McCubrey, James A.

N1 - Funding Information: We appreciate the artwork done by Ms. Catherine Spruill. We appreciate the helpful comments on this review by Dr. Joseph Cory. This work was supported in part by a grant (R01CA51025) from the National Cancer Institute and the North Carolina Biotechnology Center (9805-ARG-0006) to J.A.M. Caroline Weinstein-Oppenheimer was a recipient of a Fulbright-LASPAU scholarship, an International Peace scholarship from the Promotion of Education Organization, and an Organization of American States (OAS) scholarship.

PY - 2000

Y1 - 2000

N2 - This review focuses on the Ras-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signal transduction pathway and the consequences of its unregulation in the development of cancer. The roles of some of the cell membrane receptors involved in the activation of this pathway, the G-protein Ras, the Raf, MEK and ERK kinases, the phosphatases that regulate these kinases, as well as the downstream transcription factors that become activated, are discussed. The roles of the Ras-Raf-MEK-ERK pathway in the regulation of apoptosis and cell cycle progression are also analyzed. In addition, potential targets for pharmacological intervention in growth factor-responsive cells are evaluated.

AB - This review focuses on the Ras-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signal transduction pathway and the consequences of its unregulation in the development of cancer. The roles of some of the cell membrane receptors involved in the activation of this pathway, the G-protein Ras, the Raf, MEK and ERK kinases, the phosphatases that regulate these kinases, as well as the downstream transcription factors that become activated, are discussed. The roles of the Ras-Raf-MEK-ERK pathway in the regulation of apoptosis and cell cycle progression are also analyzed. In addition, potential targets for pharmacological intervention in growth factor-responsive cells are evaluated.

KW - ERK

KW - Growth factors

KW - MEK

KW - Raf

KW - Ras

KW - Receptors

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U2 - 10.1016/S0163-7258(00)00085-1

DO - 10.1016/S0163-7258(00)00085-1

M3 - Review article

C2 - 11337027

AN - SCOPUS:0034450953

SN - 0163-7258

VL - 88

SP - 229

EP - 279

JO - Pharmacology and Therapeutics

JF - Pharmacology and Therapeutics

IS - 3

ER -

The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors

Abstract

Keywords

ASJC Scopus subject areas

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