No role for RTK in GPCR activation of the Ras-MAPK pathway?

6 May 2010

Coralie A. C. Carraway

To my way of thinking, genetic approaches alone cannot begin to answer such critical questions as involvement of known important signaling proteins in a given pathway, especially when crosstalk is known to be involved. There are very few, if any, cases in complex organisms in which crosstalk is not involved. This holds also for simple organisms; even single-cell organisms respond to a variety of stimuli, and the vectorial responses under any set of conditions are tightly regulated by crosstalk.

Such reductionist thinking also does not take into account critically important post-transcriptional processes which are vital to cellular readout. Major players not predictable by genetics include stability of message, all posttranslational modifications, including proteolysis, stability of proteins, protein biosynthesis and turnover, and protein interactions which direct their cellular localization. Superimposed upon all of these factors are cell context considerations.

Mother Nature can be simplified only to a point; careful regulation is complex, and organismal survival depends on that complexity.