Location of cAMP-Dependent Protein Kinase Type I with the TCR-CD3 Complex

Skålhegg, Bjørn Steen; Taskén, Kjetil; Hansson, V.; Huitfeldt, Henrik S.; Jahnsen, Tore; Lea, Tor

doi:10.1126/science.8272870

Cited by 179 publications

(125 citation statements)

References 24 publications

(5 reference statements)

Supporting

Mentioning

121

Contrasting

Order By: Relevance

“…PKA type I is necessary and sufficient to confer cAMP-dependent inhibition of lymphocyte proliferation induced through the antigen receptor of T cells (26). A distinct redistribution and colocalization of PKA type I to the antigen receptors in both T cells (27) and B cells (28) is observed, supporting the notion of an isozyme-specific effect of PKA type I. Whether such direct interactions of PKA type I to receptors are limited to "mitogenic" receptors and proliferative responses or may be a general phenomenon of all antigen receptors is not known.…”

mentioning

confidence: 66%

“…PKA type I-mediated inhibition of receptor-induced B and T cell proliferation is accomplished by a distinct redistribution and localization of PKA type I to the antigen receptor complexes in these cells. PKA type II, on the other hand, localizes mainly to the centrosomes in lymphocytes and is therefore more likely to serve a completely different function in these cells (27,41). Thus, PKA type I may play an important role in all lymphoid cells as a negative regulator of receptor-induced cell proliferation and function in lymphoid cells.…”

Section: Activation Of Pkc By Tpa and Ionomycin Reverses The Inhibitomentioning

confidence: 99%

See 1 more Smart Citation

Selective Activation of cAMP-dependent Protein Kinase Type I Inhibits Rat Natural Killer Cell Cytotoxicity

Torgersen

Vaage²,

Levy

et al. 1997

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The present study examines the expression and involvement of cAMP-dependent protein kinase (PKA) isozymes in cAMP-induced inhibition of natural killer (NK) cell-mediated cytotoxicity. Rat interleukin-2-activated NK cells express the PKA ␣-isoforms RI␣, RII␣, and C␣ and contain both PKA type I and type II. Prostaglandin E 2 , forskolin, and cAMP analogs all inhibit NK cell lysis of major histocompatibility complex class I mismatched allogeneic lymphocytes as well as of standard tumor target cells. Specific involvement of PKA in the cAMP-induced inhibition of NK cell cytotoxicity is demonstrated by the ability of a cAMP antagonist, (R p )-8-Br-adenosine 3 ,5 -cyclic monophosphorothioate, to reverse the inhibitory effect of complementary cAMP agonist (S p )-8-Br-adenosine 3 ,5 -cyclic monophosphorothioate. Furthermore, the use of cAMP analog pairs selective for either PKA isozyme (PKA type I or PKA type II), shows a preferential involvement of the PKA type I isozyme, indicating that PKA type I is necessary and sufficient to completely abolish killer activatory signaling leading to NK cell cytotoxicity. Finally, combined treatment with phorbol ester and ionomycin maintains NK cell cytotoxicity and eliminates the cAMP-mediated inhibition, demonstrating that protein kinase C and Ca 2؉ -dependent events stimulate the cytolytic activity of NK cells at a site distal to the site of cAMP/PKA action.Natural killer (NK) 1 cells constitute a distinct lineage of lymphocytes (1) with the innate ability to specifically recognize and kill certain normal allogeneic leukocytes (2, 3), tumor cells, and virally infected cells (4, 5) by direct cell-mediated cytotoxicity. The presence of both activating and inhibitory NK cell receptors have been implicated in regulation of NK cytolysis. As formulated in the "missing self" hypothesis (6), a no-kill signal is induced by specific interaction of "self" MHC class I molecules with inhibitory NK receptors. Therefore, the presence of intracellular signaling pathways down-regulating or inhibiting the cytotoxic response may be important in preventing killing of normal autologous cells. In contrast to the "self" MHC class I-induced inhibition of natural killing, activating receptors have not been characterized to the same extent. However, both foreign MHC antigens on normal allogeneic cells and non-MHC antigens expressed on tumor cells have been demonstrated to interact with yet not fully characterized activating NK cell receptors (7-10). The present view is that NK cytotoxicity is a result of a fine balance between negative and positive signals induced through distinct sets of receptors inhibiting or activating the cytolytic activity (11).The second messenger cAMP regulates a number of cellular processes (12, 13). With the exception of certain ion channels, directly regulated by cAMP (14, 15), all known effects of cAMP are mediated via activation of cAMP-dependent protein kinase (PKA). The inactive PKA holoenzyme is a tetramer consisting of two regulatory (R) and two catalytic (C) subunits (16)....

show abstract

mentioning

confidence: 66%

Section: Activation Of Pkc By Tpa and Ionomycin Reverses The Inhibitomentioning

confidence: 99%

Selective Activation of cAMP-dependent Protein Kinase Type I Inhibits Rat Natural Killer Cell Cytotoxicity

Torgersen

Vaage²,

Levy

et al. 1997

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…R I ␣ is also enriched in the neuromuscular junctions (7). Type I holoenzyme is also depleted from the cytoplasm and accumulates at the ''cap'' site when lymphocytes are stimulated with anti-CD3 antibodies (8). R I was also found to associate with activated B cell receptors (9).…”

mentioning

confidence: 93%

D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain

Huang

Durick

Weiner

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

211

188

View full text Add to dashboard Cite

show abstract

“…This cAMP-dependent inhibition is mediated by the type I PKA [9]. Immunocytochemistry and immunoprecipitation studies on T lymphocytes have shown that cAMP induces the translocation of type I PKA and promotes its interaction with the antigen specific T cell receptor-CD3 complex [10]. It has been hypothesized that a type I PKA-mediated phosphorylation may induce uncoupling of TCR-CD3 complex from the intracellular transduction pathways [10].…”

Section: Introductionmentioning

confidence: 99%

“…Immunocytochemistry and immunoprecipitation studies on T lymphocytes have shown that cAMP induces the translocation of type I PKA and promotes its interaction with the antigen specific T cell receptor-CD3 complex [10]. It has been hypothesized that a type I PKA-mediated phosphorylation may induce uncoupling of TCR-CD3 complex from the intracellular transduction pathways [10]. Additional early steps in T lymphocyte activation, such as stimulation of phospholipase C and tyrosine phosphorylation of the ppl00 phosphoprotein, are inhibited by an increase in intracellular cAMP [11].…”

Section: Introductionmentioning

confidence: 99%

Identification of cyclic AMP‐phosphodiesterase variants from the PDE4D gene expressed in human peripheral mononuclear cells

Némoz¹,

Zhang²,

Sette³

et al. 1996

FEBS Letters

View full text Add to dashboard Cite

To determine whether the expression of different PDE4D variants is unique to the rat or conserved through evolution, we have characterized the different PDE4D mRNAs expressed in human peripheral blood mononuclear cells. RT-PCR was performed using primers based on rat sequences and mRNAs from mononuclear cells. The specifically amplified fragments had a size identical to that predicted for rat PDEAD1, PDE4D2 and PDE4D3. Sequencing confirmed that these fragments are derived from the human PDE4D gene. Their sequence was highly homologous to that reported for the rat variants, cDNAs corresponding to the entire ORF of human PDE4D2 and PDFAD3 were expressed in mammalian cells, causing a large increase in PDE activity. Western blot analysis of human peripheral blood mononuclear cell extracts demonstrated the presence of proteins corresponding to the recombinant PDE4D1 and PDE4D2. The pattern of splicing and different promoter usage of the PDE4D gene is therefore conserved during evolution, which indicates an important physiological role.

show abstract

Location of cAMP-Dependent Protein Kinase Type I with the TCR-CD3 Complex

Cited by 179 publications

References 24 publications

Selective Activation of cAMP-dependent Protein Kinase Type I Inhibits Rat Natural Killer Cell Cytotoxicity

Selective Activation of cAMP-dependent Protein Kinase Type I Inhibits Rat Natural Killer Cell Cytotoxicity

D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain

Identification of cyclic AMP‐phosphodiesterase variants from the PDE4D gene expressed in human peripheral mononuclear cells

Contact Info

Product

Resources

About