Sodium vanadate, a tyrosine phosphatase inhibitor, affects expression of hematopoietic growth factors and extracellular matrix RNAs in SV40-transformed human marrow stromal cells.
Protein tyrosine kinases represent a subset of proteins that mediate signal transduction between the extracellular environment and the nucleus. We have previously described a coordinated upregulation between RNA transcripts of a tyrosine kinase, c-abl, and those of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL-6) in human marrow stromal cells (SVMSC). Moreover, an inverse relationship exists between expression of c-abl transcripts and those of extracellular matrix proteins such as type collagen I transcripts. In the present study, these inverse relationships were again seen in SVMSC when tyrosine kinase effects were enhanced by treatment of the cells with the tyrosine phosphatase inhibitor sodium orthovanadate. This suggests that tyrosine kinases are involved in the coordinate regulation of these genes.
Andrews
D F
DF
Department of Medicine, Veterans Administration Medical Center, Seattle, WA 98108.
Lilly
M B
MB
Tompkins
C K
CK
Singer
J W
JW
D001854:Bone Marrow Cells; D002472:Cell Transformation, Viral; D003094:Collagen / Q000235:genetics; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression; D016313:Genes, abl; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006410:Hematopoiesis / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics; D013539:Simian virus 40; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014638:Vanadates / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014638:Vanadates; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen; D017027:Protein Tyrosine Phosphatases