ArticleAmerican journal of physiology. Cell physiology2012
Modulation of Kv1.3 channels by protein kinase A I in T lymphocytes is mediated by the disc large 1-tyrosine kinase Lck complex.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 24 citations in OpenAlex.
- NDRG1-PTEN association modulates PTEN C-terminal tail phosphorylation in insulin-resistant neurons.Molecular and cellular biochemistry · 2026Article
- Voltage-dependent potassium channel regulatory subunits in the immune system.Biophysical reviews · 2026Review
- Deviation from physiologically appropriate oxygen levels alters proliferation, cytokine production and proximal antigen receptor signalling in CD4+ memory T cells.Frontiers in immunology · 2026Article
- Evolutionary duplication of the leishmanial adaptor protein α-SNAP plays a role in its pathogenicity.The Journal of biological chemistry · 2025Article
- Dynamics and spatial organization of Kv1.3 at the immunological synapse of human CD4+ T cells.Biophysical journal · 2024Article
- The LCK-14-3-3ζ-TRPM8 axis regulates TRPM8 function/assembly and promotes pancreatic cancer malignancy.Cell death & disease · 2022Article
- Beyond TCR Signaling: Emerging Functions of Lck in Cancer and Immunotherapy.International journal of molecular sciences · 2019Review
- Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated KJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function.Frontiers in immunology · 2019Review
- Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells.Frontiers in immunology · 2018Article
- The small neurotoxin apamin blocks not only small conductance CaEuropean biophysics journal : EBJ · 2017Article
- Immunosuppressive evidence of Tityus serrulatus toxins Ts6 and Ts15: insights of a novel K(+) channel pattern in T cells.Immunology · 2016Article
- Immunosuppression by N-methyl-D-aspartate receptor antagonists is mediated through inhibition of Kv1.3 and KCa3.1 channels in T cells.Molecular and cellular biology · 2014Article
- Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- The role of PSD-95 in the rearrangement of Kv1.3 channels to the immunological synapse.Pflugers Archiv : European journal of physiology · 2013Article
- Selective inhibition of CCR7(-) effector memory T cell activation by a novel peptide targeting Kv1.3 channel in a rat experimental autoimmune encephalomyelitis model.The Journal of biological chemistry · 2012Article
- KCa3.1 and TRPM7 channels at the uropod regulate migration of activated human T cells.PloS one · 2012Article
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7 authors at 2 institutions in 1 country.
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Abstract
The cAMP/PKA signaling system constitutes an inhibitory pathway in T cells and, although its biochemistry has been thoroughly investigated, its possible effects on ion channels are still not fully understood. K(V)1.3 channels play an important role in T-cell activation, and their inhibition suppresses T-cell function. It has been reported that PKA modulates K(V)1.3 activity. Two PKA isoforms are expressed in human T cells: PKAI and PKAII. PKAI has been shown to inhibit T-cell activation via suppression of the tyrosine kinase Lck. The aim of this study was to determine the PKA isoform modulating K(V)1.3 and the signaling pathway underneath. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), a nonselective activator of PKA, inhibited K(V)1.3 currents both in primary human T and in Jurkat cells. This inhibition was prevented by the PKA blocker PKI(6-22). Selective knockdown of PKAI, but not PKAII, with siRNAs abolished the response to 8-BrcAMP. Additional studies were performed to determine the signaling pathway mediating PKAI effect on K(V)1.3. Overexpression of a constitutively active mutant of Lck reduced the response of K(V)1.3 to 8-Br-cAMP. Moreover, knockdown of the scaffolding protein disc large 1 (Dlg1), which binds K(V)1.3 to Lck, abolished PKA modulation of K(V)1.3 channels. Immunohistochemistry studies showed that PKAI, but not PKAII, colocalizes with K(V)1.3 and Dlg1 indicating a close proximity between these proteins. These results indicate that PKAI selectively regulates K(V)1.3 channels in human T lymphocytes. This effect is mediated by Lck and Dlg1. We thus propose that the K(V)1.3/Dlg1/Lck complex is part of the membrane pathway that cAMP utilizes to regulate T-cell function.
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