serine/threonine protein kinase PLK3; cytokine-inducible serine/threonine protein kinase; FGF-inducible kinase; polo-like kinase 3; PLK-3; proliferation-related kinase (PLK3, CNK, FNK, PRK)

Function

• serine/threonine-protein kinase
• role in cell cycle regulation, response to stress & Golgi disassembly
• polo-like kinases act by binding & phosphorylating proteins already phosphorylated on a specific motif recognized by the POLO box domains
• phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A & VRK1
• required for entry into S phase & cytokinesis
• phosphorylates BCL2L1, leading to regulate the G2 checkpoint & progression to cytokinesis during mitosis
• role in response to stress: rapidly activated by
  • ionizing radiation & UV radiation
  • reactive oxygen species
  • hyperosmotic stress
  • hypoxia
• role in DNA damage response & G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 & p73/TP73
• phosphorylates p53/TP53 in response to reactive oxygen species, thus promoting p53/TP53-mediated apoptosis
• phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint
• phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation & pro-apoptotic functions
  • phosphorylates HIF1A & JUN in response to hypoxia
• phosphorylates ATF2 following hyperosmotic stress in corneal epithelium
• role in Golgi disassembly during the cell cycle
  • part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1
• may participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis & cytokinesis are interrupted (characteristic of megakaryocyte differentiation) via its interaction with CIB1
• phosphorylated (ATM-dependent) following DNA damage
• phosphorylated as cells enter mitosis & dephosphorylated as cells exit mitosis
• interacts (via the POLO-box domain) with CIB1; leading to
• inhibit PLK3 kinase activity. interacts with GOLGB1

formerly

• serine/threonine protein kinase involved in regulating M phase functions during the cell cycle
• may also be part of the signaling network controlling cellular adhesion
• in vitro, is able to phosphorylate CDC25C & casein
• phosphorylated as cells enter mitosis & dephosphorylated as cells exit mitosis (putative)
• binds to the Ca+2/integrin-binding protein (CIB)
• this interaction probably occurs via the POLO-box domain

* not clear where phosphorylation occurs.

* prior edition of UniProt listed Thr-348 as phospho-Thr site

Structure

• belongs to the protein kinase superfamily, Ser/Thr protein kinase family, CDC5/polo subfamily
• contains 2 POLO box domains
• contains 1 protein kinase domain

Compartment

membrane; peripheral membrane protein

Expression

• expressed in placenta, lung > skeletal muscle, heart, pancreas, ovaries & kidney > liver & brain
• may have a short1/2 life
• in cells of hematopoietic origin, strongly & exclusively detected in terminally differentiated macrophages
• expression induced by cytokines & cellular adhesion

Pathology

• expression appears to be down-regulated in primary lung cancer

More general terms

• serine/threonine kinase
• human longevity protein

Additional terms

• CD95; Fas antigen; tumor necrosis factor receptor superfamily member 6; apo-1 antigen; apoptosis-mediating surface antigen FAS; FASLG receptor (FAS, APT1, FAS1, TNFRSF6)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1263
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1263
• OMIM: https://mirror.omim.org/entry/602913
• UniProt: http://www.uniprot.org/uniprot/Q9H4B4.html