G13alpha-mediated PYK2 activation. PYK2 is a mediator of G13alpha -induced serum response element-dependent transcription.

G(12)alpha/G(13)alpha transduces signals from G-protein-coupled receptors to stimulate growth-promoting pathways and the early response gene c-fos. Within the c-fos promoter lies a key regulatory site, the serum response element (SRE). Here we show a critical role for the tyrosine kinase PYK2 in muscarinic receptor type 1 and G(12)alpha/G(13)alpha signaling to ...
an SRE reporter gene. A kinase-inactivate form of PYK2 (PYK2 KD) inhibits muscarinic receptor type 1 signaling to the SRE and PYK2 itself triggers SRE reporter gene activation through a RhoA-dependent pathway. Placing PYK2 downstream of G-protein activation but upstream of RhoA, the expression of PYK2 KD blocks the activation of an SRE reporter gene by GTPase-deficient forms of G(12)alpha or G(13)alpha but not by RhoA. The GTPase-deficient form of G(13)alpha triggers PYK2 kinase activity and PYK2 tyrosine phosphorylation, and co-expression of the RGS domain of p115 RhoGEF inhibits both responses. Finally, we show that in vivo G(13)alpha, although not G(12)alpha, readily associates with PYK2. Thus, G-protein-coupled receptors via G(13)alpha activation can use PYK2 to link to SRE-dependent gene expression.
Mesh Terms:
Amino Acid Substitution, Animals, COS Cells, Focal Adhesion Kinase 2, GTP Phosphohydrolases, GTP-Binding Protein alpha Subunits, G12-G13, Genes, Reporter, Hela Cells, Heterotrimeric GTP-Binding Proteins, Humans, Luciferases, Mutagenesis, Site-Directed, Phosphorylation, Protein-Tyrosine Kinases, Recombinant Proteins, Sequence Deletion, Transcription, Genetic, Transfection, rhoA GTP-Binding Protein
J. Biol. Chem.
Date: Aug. 11, 2000
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