Diacylglycerol kinase, translocation

Sakane, R, Yamada, K., Imai, S., and Kanoh, H., 1991, Porcine 80-kDa diacylglycerol kinase is a calcium-binding and calcium/phospholipid-dependent enzyme and undergoes calcium-dependent translocation./.B/o/. Chem. 266 7096-7100. 

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

Fig. 7.10. Functions and regulation of protein kinase C. Receptor-controlled signal pathways lead to formation of the intracellular messenger substances and diacylglycerol (DAG), that, like phorbol ester (TPA), activate protein kinase C (PKC). Translocation to the cell membrane is linked with activation of protein kinase C receptors for protein kinase C, the RACK proteins, are also involved. Substrates of protein kinase C are the MARCKS proteins and other proteins associated with the cytoskeleton. Other substrates are the Raf kinase (see Chapter 10) and the receptor for vitamin D3 (VDR, see Chapter 4).

Fig. 11.1 Activation of MAPK pathway by Angll and ET-1 in VSMC. Stimulation of Angll and ET-1 receptors through Gq/n activation enhances the activity of PLCp. Activated PLC 3 converts PIP2 to IP3 and diacylglycerol (DAG). IP3 elevates the concentration of intracellular calcium and DAG activates PKC. PKC and/or Ca2+/calmodulin (CaM)-dependent protein kinases (CaMK) activate nonreceptor (NR) and/or receptor (R) protein tyrosine kinases. Activation of these components signals the stimulation of Ras/Raf/MEK/ERKl/2 and p70 s6k. ERK1/2 and p70 s6k are translocated to nucleus and regulate nuclear events by activating transcription factors through phosphorylation.

The atypical protein kinase is ubiquitously expressed. It is considered atypical in that it is not activated by diacylglycerol or pre-treatment with phorbol esters. In addition, the protein does not undergo translocation from cytosol to membrane when activated. Phosphatidylinositol 3,4,5-triphosphate has been shown to result in a large stimulation of protein kinase t, (Nakanishi et al. 1993). 

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