Alternative titles; symbols
HGNC Approved Gene Symbol: PKN3
Cytogenetic location: 9q34.11 Genomic coordinates (GRCh38) : 9:128,702,503-128,720,916 (from NCBI)
By PCR using degenerate primers based on the sequence of PKN (PKN1; 601032), followed by screening a HeLa cell cDNA library, Oishi et al. (1999) cloned full-length PKN3, which they called PKN-beta. The deduced 889-amino acid protein has a calculated molecular mass of 99.6 kD. PKN3 contains 3 N-terminal repeats of a charged region with leucine zipper-like sequences, followed by a domain conserved in other PKN proteins, 2 unique proline-rich regions, and a C-terminal catalytic region with a protein kinase-type ATP-binding sequence. Northern blot analysis detected a 3-kb PKN3 transcript in several cancer cell lines, but not in normal adult human tissues. Western blot analysis revealed a 110-kD Pkn3 protein in NIH3T3 mouse fibroblasts. PKN3 localized to the Golgi apparatus in NIH3T3 and human cell lines.
Oishi et al. (1999) found that in vitro translated PKN3 bound RHOA (ARHA; 165390) in a GTP-dependent manner. PKN3 also showed autophosphorylation activity that was dependent on lys588.
Using yeast 2-hybrid analysis, in vitro binding assays, and immunoprecipitation analysis, Shibata et al. (2001) showed that PKN-beta interacted with GRAF (ARHGAP26; 605370) and GRAF2 (ARHGAP10; 609746). A constitutively active form of PKN-beta phosphorylated recombinant GRAF and GRAF2. Mutation analysis showed that the linker region of PKN-beta bound to the SH3 domains of GRAF and GRAF2.
Using a combination of 3-dimensional culture conditions and gene expression profiling, Leenders et al. (2004) identified PKN3 as a mediator of malignant growth of human prostate cancer cells downstream of activated PI3K (see PIK3CG; 601232). Immunohistochemical analysis and in situ hybridization showed that PKN3 was upregulated in human tumor cells, but not in surrounding nontumorigenic tissues. Inducible knockdown of PKN3 expression inhibited metastasis in a mouse prostate tumor model. The catalytic activity of PKN3 depended upon PI3K, but not on AKT (164730).
Hartz (2007) mapped the PKN3 gene to chromosome 9q34.11 based on an alignment of the PKN3 sequence (GenBank AB019692) with the genomic sequence (build 36.1).
Hartz, P. A. Personal Communication. Baltimore, Md. 1/23/2007.
Leenders, F., Mopert, K., Schmiedeknecht, A., Santel, A., Czauderna, F., Aleku, M., Penschuck, S., Dames, S., Sternberger, M., Rohl, T., Wellmann, A., Arnold, W., Giese, K., Kaufmann, J., Klippel, A. PKN3 is required for malignant prostate cell growth downstream of activated PI 3-kinase. EMBO J. 23: 3303-3313, 2004. [PubMed: 15282551] [Full Text: https://doi.org/10.1038/sj.emboj.7600345]
Oishi, K., Mukai, H., Shibata, H., Takahashi, M., Ona, Y. Identification and characterization of PKN-beta, a novel isoform of protein kinase PKN: expression and arachidonic acid dependency are different from those of PKN-alpha. Biochem. Biophys. Res. Commun. 261: 808-814, 1999. [PubMed: 10441506] [Full Text: https://doi.org/10.1006/bbrc.1999.1116]
Shibata, H., Oishi, K., Yamagiwa, A., Matsumoto, M., Mukai, H., Ono, Y. PKN-beta interacts with the SH3 domains of Graf and a novel Graf related protein, Graf2, which are GTPase activating proteins for Rho family. J. Biochem. 130: 23-31, 2001. [PubMed: 11432776] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a002958]