Identification of a novel gene--SSK1--in human endothelial cells exposed to shear stress.
To identify transcriptionally regulated genes potentially involved in the effect of shear stress on endothelial gene expression, we performed a differential display analysis of mRNAs from human umbilical vein endothelial cell (HUVEC) exposed to laminar shear stress (12 dynes/cm2) in comparison to HUVEC maintained in static condition. We identified a cDNA fragment overexpressed by laminar shear stress. The full-length, SSK1, was 3653 long and encoded for a novel protein of 1050 amino acids. Northern blot demonstrates that SSK1 mRNA is expressed at high levels also in placenta, a weak transcript was present in heart, skeletal muscle, kidney and pancreas. Homology searches of the protein databases showed that SSK1 is related to numerous serine-threonine kinases. The highest homology was found with a very recently described gene, BUBR1, an analogue of BUB1, which is a kinase involved in the regulation of cell cycle. The most conserved residues in catalytic domains II, III, VIb, VII, VIII and IX of serine-threonine protein kinases were found in the C terminal region of SSK1 which further supports the kinase nature of the new protein. The putative serine-threonine kinase SSK1 may represent a tool by which mechanical forces regulates phosphorylation events within endothelial cells.
Donadelli
R
R
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Benatti
L
L
Remuzzi
A
A
Morigi
M
M
Gullans
S R
SR
Benigni
A
A
Remuzzi
G
G
Noris
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology*; D015870:Gene Expression; D006439:Hemodynamics; D006801:Humans; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological / Q000235:genetics*; D014018:Tissue Distribution; D014471:Umbilical Veins / Q000166:cytology
D018076:DNA, Complementary; D012333:RNA, Messenger; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases