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Question 7.6

Important examples include: Signaling cascade amplifies signals, despite noise (technical

term: noise) in the cell. Nice examples are the Ras-Raf-Mek-Erk cascade (intracellular

cascade; high signal amplification; shutdown phosphatase; disease, by B-Raf mutation

about cascade constantly on, leads to melanoma) or blood coagulation (extracellular cas­

cade; also very good signal amplification, extrinsic and intrinsic stimulus uptake, the vari­

ous clotting factors amplify the signal, finally this amplification via thrombin then produces

fibrin polymers; here it is interesting that the opposite action, the dissolution of a blood

clot, is again a cascade, via the plasminogen system).

Question 7.7

20.6

­

1 molecule Ras

10 molecules of Raf

100 molecules of Mek

1000 molecules of Erk

A 1000-fold stronger signal in the cell than at the beginning. Note: Exact data and kinetic

modeling for this cascade can be found in Robubi et al. (2005).

Question 7.8

Growth signals are passed on via this cascade to further locations in the cell, in particular

to transcription factors, which then switch on genes in the cell nucleus that then lead to cell

growth. It is important that the signal is switched off again. This generally happens through

phosphatases. A nice example is the Ras-Raf-Mek-Erk signalling pathway. Ras is a kinase

that, when activated, regulates all other downstream components of the signalling path­

way, for example Raf and Mek, and thus influences proliferation, i.e. cell growth. However,

if a mutation prevents the cellular Raf from being switched off, for example, the growth

signal remains on all the time. A biological example is melanoma. Here, a B-Raf mutation

is present, and then the cellular phosphatases can no longer switch off the cascade and set

it to zero.

Question 7.9

20.7

2005

20  Solutions to the Exercises