Sun M, Hart JR, Hillmann P, Gymnopoulos M, Vogt PK
Cell Cycle. 2011 Nov 1;10(21):3731-9. doi: 10.4161/cc.10.21.17920. Epub 2011 Nov 1.
Addition of short (6 to 16 amino acids) peptide sequences to the N-terminus of p110alpha induces a gain of function. Such sequences include the common Flag, His, and VSV tags as well as random sequences. An N-terminal myristylation signal generally believed to activate p110alpha by providing a constitutive membrane address is also activating, if myristylation is mutationally abolished. The gain of function seen with N-terminally tagged (NTT) p110alpha constructs extends to signaling, oncogenic transformation and stimulation of cell growth. The activating effect of N-terminal tags requires a functional Ras- binding domain in p110alpha. Mutations in that domain (T208D and K227A) abolish the gains of function in oncogenicity and signaling. The dominant negative mutant of Ras, RasN17, interferes with transformation induced by NTT p110alpha. In contrast, binding to p85 activity is not required for cellular transformation and enhanced signaling by NTT p110alpha.