Expression and mechanism of spleen tyrosine kinase activation by angiotensin II and its implication in protein synthesis in rat vascular smooth muscle cells

Fariborz A. Yaghini, Fang Li, Kafait Malik

Research output: Contribution to journalArticle

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Abstract

Syk, a 72-kDa tyrosine kinase, is involved in development, differentiation, and signal transduction of hematopoietic and some non-hematopoietic cells. This study determined if Syk is expressed in vascular smooth muscle cells (VSMC) and contributes to angiotensin II (Ang II) signaling and protein synthesis. Syk was found in VSMC and was phosphorylated by Ang II through AT1 receptor. Ang II-induced Syk phosphorylation was inhibited by piceatannol and dominant negative but not wild type Syk mutant. Syk phosphorylation by Ang II was attenuated by cytosolic phospholipase A2 (cPLA2) inhibitor pyrrolidine-1 and retrovirus carrying small interfering RNAs (shRNAs) of this enzyme. Arachidonic acid (AA) increased Syk phosphorylation, and AA- and Ang II-induced phosphorylation was diminished by inhibitors of AA metabolism (5,8,11,14-eicosatetraynoic acid) and lipoxygenase (LO; baicalein) but not cyclooxygenase (indomethacin). AA metabolites formed via LO, 5(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic acids, which activate p38 MAPK, increased Syk phosphorylation. p38 MAPK inhibitor SB202190, and dominant negative p38 MAPK mutant attenuated Ang II- and AA-induced Syk phosphorylation. Adenovirus dominant negative c-Src mutant abolished Ang II - and AA-induced Syk phosphorylation and SB202190, and dominant negative p38 MAPK mutant inhibited Ang II-induced c-Src phosphorylation. Syk dominant negative mutant but not epidermal growth factor receptor blocker AG1478 also inhibited Ang II-induced VSMC protein synthesis. These data suggest that Syk expressed in VSMC is activated by Ang II through p38 MAPK-activated c-Src subsequent to cytosolic phospholipase A2 and generation of AA metabolites via LO, and it mediates Ang II-induced protein synthesis independent of epidermal growth factor receptor transactivation (Ang II → cPLA2 → AA metabolites of LO → p38 MAPK → c-Src → Syk → protein synthesis).

Original languageEnglish (US)
Pages (from-to)16878-16890
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number23
DOIs
StatePublished - Jun 8 2007

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Vascular Smooth Muscle
Angiotensin II
Protein-Tyrosine Kinases
Smooth Muscle Myocytes
Muscle
Rats
Phosphorylation
Chemical activation
Cells
Arachidonic Acid
p38 Mitogen-Activated Protein Kinases
Proteins
Metabolites
Cytosolic Phospholipases A2
Epidermal Growth Factor Receptor
Syk Kinase
5,8,11,14-Eicosatetraynoic Acid
Hydroxyeicosatetraenoic Acids
Signal transduction
Lipoxygenase

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Expression and mechanism of spleen tyrosine kinase activation by angiotensin II and its implication in protein synthesis in rat vascular smooth muscle cells. / Yaghini, Fariborz A.; Li, Fang; Malik, Kafait.

In: Journal of Biological Chemistry, Vol. 282, No. 23, 08.06.2007, p. 16878-16890.

Research output: Contribution to journalArticle

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