Alternative titles; symbols
HGNC Approved Gene Symbol: PAK1IP1
Cytogenetic location: 6p24.2 Genomic coordinates (GRCh38) : 6:10,690,865-10,709,782 (from NCBI)
Using phospholipase C-beta-3 (PLCB3; 600230) as bait in a yeast 2-hybrid screen, Xia et al. (2001) cloned PIP1 from a heart cDNA library. 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 (see 139130), and PIP1 shares significant homology with yeast PAK (see PAK1; 602590) regulators. Northern blot analysis detected a major 2.4-kb PIP1 transcript in all tissues examined, with highest expression in brain, heart, and muscle. A minor 4.1-kb transcript was also detected.
Xia et al. (2001) determined that 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 (600508)-binding motif, a dimerization domain, an inhibitory switch domain, and a kinase inhibitor segment. Transfection of PIP1 in mammalian cells inhibited CDC42 (116952)-stimulated PAK kinase activity and PAK-mediated JNK (see 601158) and nuclear factor kappa-B (NFKB; see 164011) signaling pathways. Overexpression of PIP1 in mouse embryonic fibroblasts resulted in abnormally rounded cell morphology and reorganized actin stress fibers. Xia et al. (2001) proposed that PIP1 may inhibit PAK signaling by stabilizing PAK1 in the inactive dimeric conformation.
The International Radiation Hybrid Mapping Consortium mapped the PAK1IP1 gene to chromosome 6 (stSG54559).
Xia, C., Ma, W., Stafford, L. J., Marcus, S., Xiong, W.-C., Liu, M. Regulation of the p21-activated kinase (PAK) by a human G-beta-like WD-repeat protein, hPIP1. Proc. Nat. Acad. Sci. 98: 6174-6179, 2001. [PubMed: 11371639] [Full Text: https://doi.org/10.1073/pnas.101137298]