Protein kinase C[delta] differentially regulates platelet functional responses.
OBJECTIVE
Protein Kinase C delta (PKCdelta) is expressed in platelets and activated downstream of protease-activated receptors (PAR)s and glycoprotein VI (GPVI) receptors. The purpose of this study was to investigate the role of PKCdelta in platelets.


RESULTS
We evaluated the role of PKCdelta in platelets using two approaches--pharmacological and molecular genetic approach. In human platelets pretreated with isoform selective antagonistic RACK peptide (delta V1-1)TAT, and in the murine platelets lacking PKCdelta, PAR4-mediated dense granule secretion was inhibited, whereas GPVI-mediated dense granule secretion was potentiated. These effects were statistically significant in the absence and presence of thromboxane A2 (TXA2). Furthermore, TXA2 generation was differentially regulated by PKCdelta. However, PKCdelta had a small effect on platelet P-selectin expression. Calcium- and PKC-dependent pathways independently activate fibrinogen receptor in platelets. When calcium pathways are blocked by dimethyl-BAPTA, AYPGKF-induced aggregation in PKCdelta null mouse platelets and in human platelets pretreated with (delta V1-1)TAT, was inhibited. In a FeCl3-induced injury in vivo thrombosis model, PKCdelta-/- mice occluded similar to their wild-type littermates.


CONCLUSIONS
Hence, we conclude that PKCdelta differentially regulates platelet functional responses such as dense granule secretion and TXA2 generation downstream of PARs and GPVI receptors, but PKCdelta deficiency does not affect the thrombus formation in vivo.
Chari
Ramya
R
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Getz
Todd
T
Nagy
Bela
B
Bhavaraju
Kamala
K
Mao
Yingying
Y
Bynagari
Yamini Saraswathy
YS
Murugappan
Swaminathan
S
Nakayama
Keiko
K
Kunapuli
Satya P
SP
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015539:Platelet Activation / Q000502:physiology; D051745:Protein Kinase C-delta / Q000502:physiology*; D013928:Thromboxane A2 / Q000378:metabolism
D013928:Thromboxane A2; C497259:Prkcd protein, mouse; D051745:Protein Kinase C-delta