Unique functions for protein kinase D1 and protein kinase D2 in mammalian cells
Résumé
Mammalian Protein Kinase D (PKD) isoforms have been implicated in the regulation of diverse biological processes in response to diacylglycerol and Protein Kinase C (PKC) signalling. To compare the functions of PKD1 and PKD2 in vivo we generated mice deficient in either PKD1 or PKD2 enzymatic activity, via homozygous expression of PKD1Ser744Ala/Ser748Ala or PKD2Ser707Ala/Ser711Ala ‘knockin' alleles. We also examined PKD2-deficient mice generated using ‘gene trap' technology. We demonstrate that unlike PKD1, PKD2 catalytic activity is dispensable for normal embryogenesis. We also show that PKD2 is the major PKD isoform expressed in lymphoid tissues but that PKD2 catalytic activity is not essential for the development of mature, peripheral T and B lymphocytes. PKD2 catalytic activity is however required for efficient antigen receptor-induced cytokine production in T lymphocytes and for optimal T cell–dependent antibody responses in vivo. Our results reveal a key in vivo role for PKD2 in regulating the function of mature peripheral lymphocytes during adaptive immune responses. They also confirm the functional importance of PKC-mediated serine phosphorylation of the PKD catalytic domain for PKD activation and downstream signaling and reveal that different PKD family members have unique and non-redundant roles in vivo.
Origine : Fichiers produits par l'(les) auteur(s)
Loading...