

- MAPK, also known as ERK:
- Translocates to the nucleus and promotes cell division:
- When it is phosphorylated by MEK:
- A serine / threonine kinase
- When it is phosphorylated by MEK:
- Constitutive activation of this process:
- Is tumorigenic
- Translocates to the nucleus and promotes cell division:
- MAPK phosphorylation is a relatively distal step in a sequential phosphorylation cascade:
- That can begin with the activation of a tyrosine kinase:
- Is followed by phosphorylation of RAS:
- Which activates BRAF:
- A serine / threonine kinase
- Which activates BRAF:
- This is followed by MEK and MAPK phosphorylation
- Is followed by phosphorylation of RAS:
- That can begin with the activation of a tyrosine kinase:
- In papillary thyroid carcinoma:
- Somatic genetic alterations at three of these steps:
- Activate this linear signaling cascade
- Somatic genetic alterations at three of these steps:
- A gene rearrangement:
- Creating a chimeric RET or TRK activates the initial tyrosine kinase step
- Activating point mutations of either RAS or BRAF:
- Constitutively activates these proteins
- The tyrosine kinase, RAS, and BRAF genetic alterations:
- Are usually mutually exclusive, suggesting that any single alteration is sufficient to play an early role in tumorigenesis

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