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J. Biol. Chem., Vol. 277, Issue 51, 50183-50189, December 20, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/51/50183    most recent M209668200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ward, S. M. Articles by Galper, J. B. Search for Related Content PubMed PubMed Citation Articles by Ward, S. M. Articles by Galper, J. B. Social Bookmarking                      What's this?

Transforming Growth Factor  (TGF) Signaling via Differential Activation of Activin Receptor-like Kinases 2 and 5 during Cardiac Development
ROLE IN REGULATING PARASYMPATHETIC RESPONSIVENESS^*

Simone M. Ward, Jay S. Desgrosellier^§¶, Xiaoli Zhuang, Joey V. Barnett^§, and Jonas B. Galper^**

From the  Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115 and ^§ Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6400

Little is known regarding factors that induce parasympathetic responsiveness during cardiac development. We demonstrated previously that in atrial cells cultured from chicks 14 days in ovo, transforming growth factor  (TGF) decreased parasympathetic inhibition of beat rate by the muscarinic agonist, carbamylcholine, by 5-fold and decreased expression of G_i2. Here in atrial cells 5 days in ovo, TGF increased carbamylcholine inhibition of beat rate 2.5-fold and increased expression of G_i2. TGF also stimulated G_i2 mRNA expression and promoter activity at day 5 while inhibiting them at day 14 in ovo. Over the same time course expression of type I TGF receptors, chick activin receptor-like kinase 2 and 5 increased with a 2.3-fold higher increase in activin receptor-like kinase 2. Constitutively active activin receptor-like kinase 2 inhibited G_i2 promoter activity, whereas constitutively active activin receptor-like kinase 5 stimulated G_i2 promoter activity independent of embryonic age. In 5-day atrial cells, TGF stimulated the p3TP-lux reporter, which is downstream of activin receptor-like kinase 5 and had no effect on the activity of the pVent reporter, which is downstream of activin receptor-like kinase 2. In 14-day cells, TGF stimulated both pVent and p3TP-lux. Thus TGF exerts opposing effects on parasympathetic response and G_i2 expression by activating different type I TGF receptors at distinct stages during cardiac development.

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				H.-J. Park, S. M. Ward, J. S. Desgrosellier, S. P. Georgescu, A. G. Papageorge, X. Zhuang, J. V. Barnett, and J. B. Galper Transforming Growth Factor beta Regulates the Expression of the M2 Muscarinic Receptor in Atrial Myocytes via an Effect on RhoA and p190RhoGAP J. Biol. Chem., July 21, 2006; 281(29): 19995 - 20002. [Abstract] [Full Text] [PDF]