| First Author | Mayanglambam A | Year | 2011 |
| Journal | Biochem Pharmacol | Volume | 82 |
| Issue | 5 | Pages | 505-13 |
| PubMed ID | 21645497 | Mgi Jnum | J:172711 |
| Mgi Id | MGI:5008657 | Doi | 10.1016/j.bcp.2011.05.022 |
| Citation | Mayanglambam A, et al. (2011) Differential dephosphorylation of the protein kinase C-zeta (PKCzeta) in an integrin alphaIIbbeta3-dependent manner in platelets. Biochem Pharmacol 82(5):505-13 |
| abstractText | Protein kinase C-zeta (PKCzeta), an atypical isoform of the PKC family of protein serine/threonine kinases, is expressed in human platelets. However, the mechanisms of its activation and the regulation of its activity in platelets are not known. We have found that under basal resting conditions, PKCzeta has a high phosphorylation status at the activation loop threonine 410 (T410) and the turn motif (autophosphorylation site) threonine 560 (T560), both of which have been shown to be important for its catalytic activity. After stimulation with agonist under stirring conditions, the T410 residue was dephosphorylated in a time- and concentration-dependent manner, while the T560 phosphorylation remained unaffected. The T410 dephosphorylation could be significantly prevented by blocking the binding of fibrinogen to integrin alphaIIbbeta3 with an antagonist, SC-57101; or by okadaic acid used at concentrations that inhibits protein serine/threonine phosphatases PP1 and PP2A in vitro. The dephosphorylation of T410 residue on PKCzeta was also observed in PP1cgamma null murine platelets after agonist stimulation, suggesting that other isoforms of PP1c or another phosphatase could be responsible for this dephosphorylation event. We conclude that human platelets express PKCzeta, and it may be constitutively phosphorylated at the activation loop threonine 410 and the turn motif threonine 560 under basal resting conditions, which are differentially dephosphorylated by outside-in signaling. This differential dephosphorylation of PKCzeta might be an important regulatory mechanism for platelet functional responses. |
