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Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
Prostaglandin E2 activates HPK1 kinase activity via a PKA-dependent pathway
Sansana Sawasdikosol1, Saiju Pyarajan, Saba Alzabin
1New York University School of Medicine, New York University Cancer Institute, New York, New York 10016-6402, USA. sawasdik@saturn.med.nyu.edu
The Journal of Biological Chemistry
|September 27, 2007
Summary
Prostaglandin E(2) (PGE(2)) activates Hematopoietic progenitor kinase 1 (HPK1) in T cells through a novel cyclic adenosine monophosphate-dependent pathway, independent of T-cell receptor signaling molecules. This finding reveals a new mechanism for inhibiting T cell activation.
Area of Science:
- Immunology
- Cell Signaling
- Biochemistry
Background:
- Hematopoietic progenitor kinase 1 (HPK1) is a key kinase in T cell signaling.
- Prostaglandin E(2) (PGE(2)) is an immunosuppressive eicosanoid known to affect T cell function.
Purpose of the Study:
- To elucidate the signaling pathway by which PGE(2) activates HPK1 in T cells.
- To determine if this activation mechanism differs from T-cell receptor (TCR)-induced HPK1 activation.
Main Methods:
- Investigated HPK1 activation by PGE(2) in T cells.
- Assessed the role of phosphotyrosine-based signaling molecules (Lck, ZAP-70, SLP-76, Lat) in PGE(2)-induced HPK1 activation.
- Utilized site-directed mutagenesis (Serine 171 to Alanine) and PKA-deficient cell lines (S49) to study the involvement of PKA.
Main Results:
- PGE(2) activates HPK1 independently of TCR signaling components like Lck, ZAP-70, SLP-76, and Lat.
- PGE(2)-induced HPK1 activation is mediated by a 3 -5 -cyclic adenosine monophosphate-regulated, PKA-dependent pathway.
- Mutation of Serine 171, a PKA phosphorylation site, abrogated PGE(2) responsiveness, and PKA-deficient cells showed no response to PGE(2).
Conclusions:
- PGE(2) activates HPK1 via a distinct PKA-dependent pathway, separate from the canonical TCR signaling cascade.
- This pathway allows PGE(2) to inhibit T cell activation by engaging HPK1, a known negative regulator of TCR signaling.
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