Thursday 21 May 2009
ERK1/2 mitogen-activated protein kinase pathway
The Ras-dependent extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway plays a central role in cell proliferation control.
The p44/42 MAP Kinase pathway consists of a protein kinase cascade linking growth and differentiation signals with transcription in the nucleus.
Growth factor receptors and tyrosine kinases activate Ras which in turn activates c-Raf, MEK, and MAP kinase. Activated p44/42 MAP Kinase translocates to the nucleus and activates transcription by phosphorylation of kinases such as p90 RSK, MSK, and transcription factors such as ELK-1 and Stat3.
The importance of this pathway in both growth control and development has been demonstrated via the transforming properties of various mutant forms of Ras, Raf, MEK and by their effects on development.
Signal amplification and the potential for crosstalk appear to be important features of this regulatory network.
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.
- The EGFR/ERK pathway is activated in high-grade MECs with aggressive behaviour.
- Patients with these tumours who require oncological treatment in addition to surgery could benefit from EGFR and mitogen-activated protein kinase pathway inhibitors.
|HRAS||RAF1||MAP2K1 (MEK1)||MAP2K2 (MEK2)||MAPK3 (ERK1)||MAPK1 (ERK2)|
|RPS6KA5 (MSK1)||RPS6KA1 (P90RSSK)||MKNK1 (MINK1)||MKNK2 (MINK2)||MYC||ELK1||STAT3||EST1||EST2|