The role of protein kinase A anchoring via the RIIα regulatory subunit in the murine immune system

Robynn V. Schillace, Sarah F. Andrews, Sarah G. Galligan, Kimberly A. Burton, Holly J. Starks, H. G.Archie Bouwer, G. Stanley McKnight, Michael P. Davey, Daniel W. Carr

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Intracellular cAMP may inhibit T cell activation and proliferation via activation of the cAMP-dependent protein kinase, PKA. PKA signaling is maintained through interactions of the regulatory subunit with A-kinase anchoring proteins (AKAPs). We demonstrated that T cells contain AKAPs and now ask whether PKA anchoring to AKAPs via the RIIα regulatory subunit is necessary for cAMP-mediated inhibition of T cell activation. We studied the immune systems of mice lacking the RIIα regulatory subunit of PKA (-/-) and the ability of cells isolated from these mice to respond to cAMP. Dissection of spleen and thymus from wild-type (WT) and -/- mice, single cell suspensions generated from these organs, and iow cytometry analysis illustrate that the gross morphology, cell numbers, and cell populations in the spleen and thymus of the -/- mice are similar to WT controls. In vitro, splenocytes from -/- mice respond to anti-CD3/anti-CD28 and PMA/ionomycin stimulation and produce IL-2 similar to WT. Cytokine analysis revealed no significant difference in Th1 or Th2 differentiation. Finally, equivalent frequencies of CD8+ IFN-γ producing effector cells were stimulated upon infection of WT or -/- mice with Listeria monocytogenes. These data represent the first study of the role of RIIα in the immune system in vivo and provide evidence that T cell development, homeostasis. and the generation of a cell-mediated immune response are not altered in the RIIa -/- mice, suggesting either that RIIα is not required for normal immune function or that other proteins are able to compensate for RIIa function.

Original languageEnglish (US)
Pages (from-to)6847-6853
Number of pages7
JournalJournal of Immunology
Volume174
Issue number11
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Schillace, R. V., Andrews, S. F., Galligan, S. G., Burton, K. A., Starks, H. J., Bouwer, H. G. A., McKnight, G. S., Davey, M. P., & Carr, D. W. (2005). The role of protein kinase A anchoring via the RIIα regulatory subunit in the murine immune system. Journal of Immunology, 174(11), 6847-6853.