Abstract
The Ras-dependent extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway plays a central role in cell proliferation control. In normal cells, sustained activation of ERK1/ERK2 is necessary for G1- to S-phase progression and is associated with induction of positive regulators of the cell cycle and inactivation of antiproliferative genes. In cells expressing activated Ras or Raf mutants, hyperactivation of the ERK1/2 pathway elicits cell cycle arrest by inducing the accumulation of cyclin-dependent kinase inhibitors. In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells. We also highlight the findings obtained from gene disruption studies.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Cell Proliferation
-
Enzyme Activation / genetics
-
Enzyme Activation / physiology
-
G1 Phase / genetics
-
G1 Phase / physiology*
-
Humans
-
MAP Kinase Signaling System / genetics
-
MAP Kinase Signaling System / physiology*
-
Mitogen-Activated Protein Kinase 1 / deficiency
-
Mitogen-Activated Protein Kinase 1 / genetics
-
Mitogen-Activated Protein Kinase 1 / metabolism
-
Mitogen-Activated Protein Kinase 1 / physiology*
-
Mitogen-Activated Protein Kinase 3 / deficiency
-
Mitogen-Activated Protein Kinase 3 / genetics
-
Mitogen-Activated Protein Kinase 3 / metabolism
-
Mitogen-Activated Protein Kinase 3 / physiology*
-
S Phase / genetics
-
S Phase / physiology*
Substances
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3