PKN1
Domain
The C1 domain does not bind the diacylglycerol (DAG).
Function
PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.
Post-translational modifications
Autophosphorylated; preferably on serine. Phosphorylated during mitosis.
Activated by limited proteolysis with trypsin.
(Microbial infection) In case of infection, polyubiquitinated by the bacterial E3 ubiquitin-protein ligase SspH1, leading to its proteasomal degradation.
Sequence Similarities
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Tissue Specificity
Found ubiquitously. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas. Expressed in numerous tumor cell lines, especially in breast tumor cells.
Cellular localization
- Cytoplasm
- Nucleus
- Endosome
- Cell membrane
- Peripheral membrane protein
- Cleavage furrow
- Midbody
- Associates with chromatin in a ligand-dependent manner. Localization to endosomes is mediated via its interaction with RHOB. Association to the cell membrane is dependent on Ser-377 phosphorylation. Accumulates during telophase at the cleavage furrow and finally concentrates around the midbody in cytokinesis.
Alternative names
PAK1, PKN, PRK1, PRKCL1, PKN1, Serine/threonine-protein kinase N1, Protease-activated kinase 1, Protein kinase C-like 1, Protein kinase C-like PKN, Protein kinase PKN-alpha, Protein-kinase C-related kinase 1, Serine-threonine protein kinase N, PAK-1