PYK2 expression and phosphorylation in neonatal and adult cardiomyocytes

Allison L. Bayer, Alan G. Ferguson, Pamela A. Lucchesi, Allen M. Samarel

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Prolinerich tyrosine kinase (PYK2) is a Ca2--dependent, non-receptor protein tyrosine kinase involved in growth factor signaling. Although PYK2 is expressed in a variety of tissues, it has not yet been identified in cardiac muscle. Therefore, immunocytochemical and Western blotting techniques were used to examine PYK2 expression and phosphorylation in neonatal and adult rat ventricular cardiomyocytes (NRVM and ARVM, respectively). PYK2 concentration was much greater in neonatal, than in adult ventricular tissue and cardiomyocytes. In cultured cells, PYK2 expression was highly dependent on [Ca2+]i transients and contractile activity. Non-contracting, low-density NRVM in serum-free culture expressed very low levels of PYK2, while high-density, spontaneously contracting NRVM showed a ∼ 12-fold increase in PYK2 expression. Conversely, high-density NRVM treated with nifedipine (10 μM, 48 h) to block spontaneous [Ca2+]i, transients anal contractile activity resulted in a 2.6-fold decrease in PYK2 levels. Similarly, overnight culture of quiescent ARVM markedly reduced PYK2 levels. Chronic treatment (48 h) of cultured NRVM with the hypertrophic agonist endothelin-1 (ET) (10-300 nM) did not significantly increase PYK2 levels, but strongly shifted the ratio of phosphorylated to total PYK2, indicating that PYK2 phosphorylation accompanies cardiomyocyte hypertrophy. Endothelin-1 also acutely activated PYK2 in both cultured NRVM, and in freshly isolated ARVM. These results suggest that PYK2 is involved in the generation of certain aspects of cardiomyocyte hypertrophy.

Original languageEnglish (US)
Pages (from-to)1017-1030
Number of pages14
JournalJournal of Molecular and Cellular Cardiology
Volume33
Issue number5
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Calcium
  • Endothelin
  • Hypertrophy
  • Signal transduction
  • Tyrosine kinases

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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