Regulation and Function of Protein Kinase D Signaling

摘要: Protein kinase D (PKD) is an evolutionarily conserved protein with structural, enzymological, and regulatory properties different from the PKC family members. The most distinct characteristics of PKD are presence a catalytic domain distantly related to Ca2+-regulated kinases pleckstrin homology (PH) that regulates enzyme activity. N-terminal region also contains tandem repeat cysteine-rich, zinc finger-like motifs which confer high affinity binding phorbol esters repress subsequent identification PKD2 PKD3, similar in overall structure amino acid sequence PKD, confirmed notion founding member new kinases, now classified mammalian kinome within Ca2+/calmodulin-dependent (CaMK) group. can be activated intact cells by multiple stimuli acting through receptor-mediated pathways. Rapid activation has been demonstrated response G protein-coupled receptor agonists, growth factors, cross-linking B-cell T-cell cellular stress. phosphorylation Ser744 Ser748 loop critical for its activation. PKC-dependent followed late, PKC-independent, phase induced agonists Gq-coupled receptors. Accumulating evidence suggest plays role processes activities, including signal transduction, chromatin organization, Golgi function, gene expression, immune regulation, cardiac hypertrophy cell survival, adhesion, motility, polarity, DNA synthesis proliferation. studies on regulation function reviewed here illustrate remarkable diversity both generation distribution potential complex interactions downstream In conclusion, emerges as key node transduction.