Nucleocytoplasmic shuttling of STK16 (PKL12), a Golgi-resident serine/threonine kinase involved in VEGF expression regulation

Journal Article · Sun Jan 15 04:00:00 EST 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.10.010· OSTI ID:20775329

Guinea, Barbara ^[1]; Ligos, Jose Manuel ^[1]; Lain de Lera, Teresa ^[1]; Martin-Caballero, Juan ^[2]; Flores, Juana ^[3]; Garcia-Castro, Javier ^[1]; Bernad, Antonio ^[1]

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1. Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia/CSIC, Universidad Autonoma de Madrid, Campus de Cantoblanco, E-28049 Madrid (Spain)
2. Servicio de Animalario, Centro Nacional de Biotecnologia/CSIC, Universidad Autonoma de Madrid, Campus de Cantoblanco, E-28049 Madrid (Spain)
3. Departamento de Patologia Animal II, Facultad de Veterinaria, Universidad Complutense de Madrid, E-28040 Madrid (Spain)

PKL12/STK16 protein is the first identified mammalian member of a ser/thr kinase subfamily that is conserved across several kingdoms, with a broad expression pattern in murine tissues and cell types. Endogenous STK16 subcellular localization was evaluated by indirect immunofluorescence in NIH/3T3 and NRK cells, demonstrating a Golgi-associated pattern that appears to be independent of signals provided by integrin pathways. When cells were treated with brefeldin A (BFA) or nocodazole, drugs that promote Golgi disorganization, we observed STK16 translocation to the nuclear compartment. Constitutive overexpression of this protein by retroviral vectors also promotes accumulation of STK16 in the nuclear compartment, as shown by subfractionation studies. A kinase-dead STK16 mutant (E202A) was used to demonstrate that both the Golgi association and the nuclear translocation capabilities seem to be independent of the STK16 kinase activity. In addition, we show that STK16 overexpression in several cell lines enhances their capacity to produce and secrete VEGF. To confirm these data in vivo, we injected tumor cells overexpressing STK16 into immunodeficient BALBc/SCID mice. HT1080-derived tumors overexpressing STK16 showed increased volume and number of blood vessels compared to controls. Altogether, these data concur with previous reports suggesting a potential role for STK16 as a transcriptional co-activator.

• OSTI ID: 20775329
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 312; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLOOD VESSELS
DRUGS
GENE REGULATION
IN VIVO
MICE
MUTANTS
NEOPLASMS
PROTEINS
SERINE
THREONINE
TRANSLOCATION
TUMOR CELLS