Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UNIPROT:P51812 (
mitogen-activated protein
)
10,636
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thrombospondin (TSP)-1, a multidomain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. However, little is known about the mechanisms regulating its expression and release. In this article, we report that purinergic signaling participates in the production and secretion of
TSP-1
. Treatment of primary cultures of rat cortical astrocytes with extracellular ATP caused an increase in
TSP-1
expression in a time- and concentration-dependent manner and was inhibited by antagonists of P2 and P1 purinergic receptors. Agonist studies revealed that UTP, but not 2',3'-O-(4-benzoyl)benzoyl-ATP, 2-methylthio-ADP, adenosine, or 5'-N-ethyl-carboxamidoadenosine, caused a significant increase in
TSP-1
expression. In addition, release of
TSP-1
was stimulated by ATP and UTP but not by 2-methylthio-ADP or adenosine. Additional studies indicated that P2Y(4) receptors stimulate both
TSP-1
expression and release. P2Y receptors are coupled to protein kinase cascades, and signaling studies demonstrated that blockade of
mitogen-activated protein
kinases or Akt inhibited ATP- and UTP-induced
TSP-1
expression. Using an in vitro model of CNS trauma that stimulates release of ATP, we found that
TSP-1
expression increased after mechanical strain and was completely blocked by a P2 receptor antagonist and by inhibition of p38/mitogen-activated protein kinase and Akt, thereby indicating a major role for P2 receptor/protein kinase signaling in
TSP-1
expression induced by trauma. We conclude that
TSP-1
expression can be regulated by activation of P2Y receptors, particularly P2Y(4), coupled to protein kinase signaling pathways and suggest that purinergic signaling may be an important factor in
TSP-1
-mediated cell-matrix and cell-cell interactions such as those occurring during development and repair.
...
PMID:Purinergic signaling induces thrombospondin-1 expression in astrocytes. 1675 56
