title: Stimulus-induced phosphorylation of PKC theta at the C-terminal hydrophobic-motif in human T lymphocytes.
abstract: Protein kinase C (PKC) is a family of serine/threonine kinases whose activity is controlled, in part, by phosphorylation on three conserved residues that are located on the catalytic domain of the enzyme, known as the activation-loop, the turn-motif, and the C-terminal hydrophobic-motif sites. Using a panel of phospho-specific antibodies, we have determined that PKC beta(I) and delta are constitutively phosphorylated on all three sites in unstimulated and activated T cells. Although PKC theta is constitutively phosphorylated at the activation-loop and turn-motif sites in T cells, PMA or anti-CD3/CD28 stimulation results in an increase in phosphorylation at the hydrophobic-motif (Ser695), an event that coincides with translocation of the enzyme from the cytosol/cytoskeleton to the membrane. Studies on the stimulus-induced phosphorylation of PKC theta demonstrate that an upstream kinase activity involving a conventional PKC isoform(s) and the PI3-kinase pathway, rather than autophosphorylation or the rapamycin-sensitive mTOR pathway, regulates this site in T lymphocytes. However, hydrophobic-motif phosphorylation does not appear to control membrane translocation, suggesting that this site may control other aspects of PKC theta signalling.
authors: Department of Biochemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.
authors: Michael
authors: M
authors: Freeley
authors: Yuri
authors: Y
authors: Volkov
authors: Dermot
authors: D
authors: Kelleher
authors: Aideen
authors: A
authors: Long
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C