PKC inhibitors: potential in T cell-dependent immune diseases.
The basic mechanisms of serine/threonine protein kinase signaling networks have been elucidated in the past decade. Members of the protein kinase C (PKC) family are crucial in T cell signaling pathways. Particularly, PKC alpha, PKC beta, and PKC theta isotypes determine the nature of lymphocyte-specific in vivo effector responses. Therefore, PKC isotypes are validated drug targets in adaptive immunity. Selective PKC kinase inhibitors have been discovered and are currently in clinical development, where they may provide new therapeutic options for different immune disorders. Here we review the topic of PKC pathway activity in the regulation of T lymphocytes both in the cytokine response and adhesive capacity, and review recent results with PKC inhibitors in vitro and in vivo.
Baier
Gottfried
G
Department for Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria. Gottfried.Baier@i-med.ac.at
Wagner
Jürgen
J
D002448:Cell Adhesion / Q000502:physiology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology*; D007527:Isoenzymes / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology
D016207:Cytokines; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C