Adding membrane signal to cytoplasmic protein

[Cornelius Krasel]

Kevin Pumiglia (pumiglk at aa.wl.com) wrote:

[about adding CAAX to the C terminus of soluble proteins to make them
 membrane-bound]

> This approach has been used successfully.  Several times in Ras related
> studies and more recently two papers this spring (June issues of Science
> and or Nature, I can't recall the exact rteferneces right now) this
> approach was used to Target Raf-1, a cytoplasmic kinase, to the membrane. 
> The C-terminal portion (last 20 amino acids) of the K-Ras molecule has both
> a polybasic domain and a farnesylation motif(CAAX).  Both are required for
> membrane targeting.   In H-Ras, the polybasic domain is replaced by a
> myristilation sequence; again both are neccessary for full membrane
> localization.

Sos has also been targeted to the cell membrane by CAAX addition; see:

A. Aronheim, D. Engelberg, N. Li, N. Al-Alawi, J. Schlessinger, M. Karin:
Membrane Targeting of the Nucleotide Exchange Factor Sos Is Sufficient for
Activating the Ras Signaling Pathway.
Cell 78, 949-961, 1994.

--Cornelius.

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