Unique functions for protein kinase D1 and protein kinase D2 in mammalian cells

Sharon A. Matthews, Maria N. Navarro, Linda V. Sinclair, Elizabeth Emslie, Carmen Feijoo-Carnero, Doreen A. Cantrell

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    48 Citations (Scopus)

    Abstract

    Mammalian PKD (protein kinase D) isoforms have been implicated in the regulation of diverse biological processes in response to diacylglycerol and PKC (protein kinase C) 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 PKD1(S744A/S7484) or PKD2(S707A/S711A) 'knockin' alleles. We also examined PKD2-deficient mice generated using 'gene-trap' technology. We demonstrate that, unlike PKD I, 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 signalling and reveal that different PKD family members have unique and non-redundant roles in vivo.

    Original languageEnglish
    Pages (from-to)153-163
    Number of pages11
    JournalBiochemical Journal
    Volume432
    DOIs
    Publication statusPublished - 15 Nov 2010

    Keywords

    • Cytokine
    • Lymphocyte
    • Protein kinase C (PKC)
    • Protein kinase D (PKD)
    • T-cell antigen receptor (TCR)
    • NF-KAPPA-B
    • D-Mediated phosphorylation
    • In vivo
    • Neurotensin secretion
    • Signaling pathway
    • Antigen receptor
    • T-cells
    • D PKD
    • Activation
    • Transport

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