The Novel Functions of the PLC/PKC/PKD Signaling Axis in G Protein-Coupled Receptor-Mediated Chemotaxis of Neutrophils

Figure 3

PKD, a direct effector of the PLC/PKC axis, is required for neutrophil chemotaxis. (a) Scheme shows the domain compositions of the three isoforms of the PKD family, PKD1–3. All three PKD isoforms have a conserved N-terminal C1A-C1B-AC-PH domain connected to a serine/threonine kinase domain at the C-terminal. The C1A domain binds to DAG for membrane targeting, while the C1B domain has a higher affinity for phorbol ester. C1A and C1B domains are separated by a long spacer, an acidic amino-acid-rich region (AC domain). The PH domain seals the kinase domain of PKD1 and inhibits its kinase activity. PKD1 also contains an alanine- and proline-rich region (AP domain) in its N-terminus while PKD2 has a proline-rich region (P domain) in its N-terminus. (b) PKD localizes at the backside leading edge of chemotaxis cells. HL60 cells expressing PKD1-GFP (Green) chemotax in 100 nM fMLP gradient (Red). In order to visualize the gradient, 100 nM fMLP was mixed with fluorescent dye Alexa 594. A differential interference contrast (DIC) image is also shown in order to portray the protrusion area of the leading edge. (c) Scheme shows the signaling pathways in which PKD1 phosphorylates cofilin phosphatase SSH2, ultimately regulating cofilin activity in GPCR-mediated neutrophil chemotaxis.

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