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. 2016 Apr;57(4):523-5.
doi: 10.1194/jlr.C067074. Epub 2016 Feb 6.

Lipid signaling in keratinocytes: Lipin-1 plays a PArt

Wendy B Bollag  1
Affiliations

Lipid signaling in keratinocytes: Lipin-1 plays a PArt

Wendy B Bollag. J Lipid Res. 2016 Apr.
No abstract available

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Figures

Fig. 1.
Fig. 1.
The role of Lipin-1 in the regulation of cell processes. Phosphatidic acid (PA) produced as a result of the hydrolysis of phosphatidylcholine (PC) by phospholipase D (PLD) can be dephosphorylated by lipin-1 (LPIN1) to yield diacylglycerol (DAG). DAG can also be produced by the action of phospholipase C (PLC) on phosphatidylinositol 4,5-bisphosphate (PIP2) or can be phosphorylated to PA by DAG kinase (not shown). DAG acts as a second messenger to activate several effector enzymes, as shown: classical and novel protein kinase C (PKC) isoenzymes; Ras guanine nucleotide releasing protein (RasGRP), a guanine nucleotide exchange factor for Ras; chimaerins, Rac GTPase-activating proteins; protein kinase D (PKD), a serine/threonine protein kinase with homologies to PKCs and calcium/calmodulin-dependent protein kinases; and the UNC13 proteins, involved in vesicle maturation and exocytosis. The DAG produced by lipin-1 also serves as a precursor for the synthesis of triacylglycerol (TAG) and the phospholipids PC and phosphatidylethanolamine (PE). PA is also a lipid second messenger with effector enzymes as shown: phosphatidylinositol 4-phosphate 5-kinase (PI4P5K), which catalyzes the final step in the synthesis of PIP2; cRaf, a mitogen-activated protein kinase kinase kinase; mammalian target of rapamycin (mTOR), a protein kinase; Src homology region 2 domain-containing phosphatase-1 (SHP1), a tyrosine phosphatase; ribosomal p70 S6 kinase, a protein kinase; Rac, a small GTP-binding protein; phosphodiesterase D (PDE4D3), a cAMP-hydrolyzing enzyme; protein phosphatase-1 (PP1), a serine/threonine protein phosphatase; kinase suppressor of ras (KSR), a protein kinase; steroidogenic factor-1 (SF1), a nuclear hormone receptor; PKC-a; son of sevenless (SOS), a Ras guanine nucleotide exchange factor; Goa, the a subunit of a heterotrimeric G protein; KcsA, a potassium channel; sphingosine kinase-1 (SK1), an enzyme that produces the lipid signal sphingosine 1-phosphate; PKC-ζ; NADPH oxidase, a superoxide-generating enzyme; and PLCγ, a PIP2-hydrolyzing enzyme. Lipin-1 can also act as a coactivator with peroxisome proliferator-activated receptor γ coactivator 1-a (PGC-1a) and peroxisome proliferator-activated receptor-a (PPARa) to regulate gene expression, particularly of genes involved in lipid metabolism.
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