RGD Reference Report - Expression of VACM-1/cul5 mutant in endothelial cells induces MAPK phosphorylation and maspin degradation and converts cells to the angiogenic phenotype. - Rat Genome Database

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Expression of VACM-1/cul5 mutant in endothelial cells induces MAPK phosphorylation and maspin degradation and converts cells to the angiogenic phenotype.

Authors: Buchwalter, A  Van Dort, C  Schultz, S  Smith, R  Le, IP  Abbott, JL  Oosterhouse, E  Johnson, AE  Hansen-Smith, F  Burnatowska-Hledin, M 
Citation: Buchwalter A, etal., Microvasc Res. 2008 Mar;75(2):155-68. Epub 2007 Sep 4.
RGD ID: 2301431
Pubmed: PMID:17950367   (View Abstract at PubMed)
DOI: DOI:10.1016/j.mvr.2007.08.004   (Journal Full-text)

Vasopressin-activated calcium mobilizing receptor (VACM-1) is a member of the cullin gene family involved in ubiquitin-proteosome dependent regulation of cellular functions. Expression of VACM-1 cDNA in cos-1 cells in vitro decreases basal cAMP levels and inhibits growth. The expression of (S730A)VACM-1 mutant cDNA, which removes PKA-dependent phosphorylation site in the VACM-1 cDNA sequence, reverses this phenotype. Since the expression of VACM-1 protein in vivo localizes largely to the vascular endothelial cells, in this study, we examined the effects of (S730A)VACM-1 cDNA expression on cellular signaling in the rat endothelial cell line RAMEC. Our results indicate that expression of (S730A)VACM-1 cDNA in RAMEC promotes cellular proliferation and induces angiogenic growth patterns. Western blot analyses indicate that (S730A)VACM-1 cDNA transfected cells express increased levels of Nedd8 modified VACM-1 and have higher levels of phosphorylated MAPK protein when compared to controls. Furthermore, expression of (S730A)VACM-1 cDNA induces translocation of the endogenous early response gene, egr-1, to the nucleus and leads to morphological changes that involve actin rearrangement. Finally, expression of (S730A)VACM-1 cDNA in RAMEC decreases concentration of maspin, a putative anti-angiogenic factor with a tumor suppressor activity. These results show that VACM-1 protein regulates endothelial cell growth and may modulate angiogenesis by a mechanism that involves MAPK phosphorylation, nuclear localization of egr-1, maspin expression, and actin polymerization.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein neddylation  IDA 2301431 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nedd8  (NEDD8 ubiquitin like modifier)

Objects referenced in this article
Gene Cul5 cullin 5 Rattus norvegicus

Additional Information