p21 Activated Protein Kinase Interacting Protein 1 (PAK1IP1)

PIP1 binds PAK1 in vitro and in vivo. Mutation analysis indicated that PIP1 interacts specifically with the N-terminal regulatory domain of PAK1, which contains the NCK-binding motif, a dimerization domain, an inhibitory switch domain, and a kinase inhibitor segment. Transfection of PIP1 in mammalian cells inhibited CDC42-stimulated PAK kinase activity and PAK-mediated JNK and nuclear factor kappa-B (NFKB) signaling pathways.The deduced 392-amino acid protein contains 5 WD repeats in its N-terminal half and has a positively charged C-terminal domain. The WD repeats are similar to those of G protein beta subunits, and PIP1 shares significant homology with yeast PAK regulators. Northern blot analysis detected a major 2.4-kb PIP1 transcript in all tissues examined, with highest expression in brain, heart, and muscle.