New Insights Into the Diacylglycerol Signaling Network in Health and Disease

Dear Colleagues, 

Diacylglycerol (DAG) is a class of neutral lipids with two fatty acid chains attached to a glycerol backbone. It is both an intermediate in various lipid biosynthetic pathways and a critical signaling lipid for a plethora of metabolic and signaling pathways in cells. The most well-known DAG, sn-1,2-diacylglycerol, is a key second messenger generated in response to the activation of G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) which play a central role in relaying signals from the cell surface to the cell interior. The second messenger DAG binds to a highly conserved cysteine-rich zinc-finger-like motif called C1 domain which is present in a group of functionally and structurally diverse protein families. These include the serine/threonine protein kinase family protein kinase C (PKC) and D (PKD), the Rac GTPase activating protein family chimaerin, the Ras GTP exchange factor family RasGRP, the Unc-13 family which is important for synaptic transmission, the myotonic dystrophy-related Cdc42-binding kinases (MRCKs) which regulate the dynamics of the actin-myosin cytoskeleton, and the DAG kinases (DGKs) which phosphorylate DAG and generate another second messenger, phosphatidic acid (PA). These groups of proteins all bind DAG and its analogs, including the natural product phorbol esters, with high affinity; their activities and functions are critically regulated by the binding of DAG in various cellular context and locations.

Since the discovery of the first DAG target PKC four decades ago, our understanding of the complex signaling network of DAG has grown exponentially. Intense research has been devoted to the study of PKC and later to PKD, the two primary intracellular targets of DAG, in normal physiologies and diseases. These efforts have led to many new exciting discoveries, including the paradigm shift revelation that PKC functions as a tumor suppressor rather than an oncogene as many have believed. Emerging evidence has also shed new lights on the function and signaling mechanisms of other DAG targets, such as DGKs. We now know that these important DAG-binding proteins are not only key mediators of normal cell functions, but also play essential roles in many pathological conditions and diseases, including cancer, metabolic diseases, neurological disorders, inflammatory conditions, and immune dysregulations.

This Special Issue will present a collection of recent advances and new cutting-edge research on better understanding of the DAG signaling network and its function in human health and disease. Research on the discovery and development of novel modulators of DAG-binding proteins and signaling pathways will also be covered. Both original articles and comprehensive reviews within the scope of this topic in this complex evolving field are welcome.

Dr. Qiming Jane Wang
Guest Editor

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• diacylglycerol
• phorbol esters
• PKC
• PKD
• chimaerin
• RasGRP
• Unc-13
• MRCK
• DGK
• signaling transduction
• biology
• health
• disease
• therapy
• drug discovery
• drug development