Page 53 - 85 cell signalling pathways

Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 53

Module 2: Figure InsP 3 /DAG recycling
Stimulus
Plasma inositol +
Na
SMIT1
PtdIns PtdIns4P PtdIns4,5P 2 PLC DAG DAG MAG (2-AG)
DAG lipase
1 4
2 kinase
MAG 7
InsP 3 + lipase
G-6-PO 4 Ca 2+
Valproate InsP 3 InsP 3
- Pase kinase
Inositol Glycerol
synthase Arachidonic
PITP acid
de novo InsP 2 InsP 4 PA
synthesis
Lithium InsP 1 3 Recycling
-
-Inositol
monophosphatase
PITP
PtdIns Dietary
inositol
Inositol
CTP
6
PtdIns PtdIns 5 CDP.DAG CDP.DAG PA
synthetase synthetase
Endoplasmic reticulum

Inositol 1,4,5-trisphosphate (InsP 3 ) and diacylglycerol (DAG) recycling.
The cell has access to three sources of inositol. It can be synthesized de novo from glucose 6-phosphate (G-6-PO 4 ) by an inositol synthase, it
can come into the cell from the plasma using a sodium-dependent myo-inositol cotransporter-1 (SMIT1) or it can be obtained by recycling InsP 3 .
Agonist-dependent inositol lipid metabolism occurs through a series of steps as outlined in the text.

Module 2: Figure PLC structure and function

EF hands
PLC 1 - 4) PH X Y C2

PLC (1, 2) PH X SH2 SH2 SH3 Y
PLC (1 - 4) PH X Y C2

PLC RasGEF PH X Y C2 RA RA
EF hands
PLC X Y C2

GPCR PLC PLC PTKR PLC PLC
PH PH PH
G C2 G C2 RA PH C2
EF EF SH2 P P EF
Gq XY BLNK P XY + RA EF XY
XY SH2 P RasGEF
P Ras
+
G G IP Translocation IP
3 IP 3 Ca 2+ IP 3 3
+
Ca 2+ PH Ca 2+ Ca 2+ Ca 2+
EF SH2
XY SH2

The domain structure and activation mechanisms of PLC isoforms.
The pleckstrin homology (PH) domain, four EF-hand domains, the catalytic X and Y domains, and the C2 domain are a common feature of most of
the PLC isoforms. The two PLCγ isoforms differ from the others by lacking a C2 domain and by having additional domains such as the Src homology
2 (SH2) and Src homology 3 (SH3) domains located between a split PH domain. The black triangles indicate the sites of tyrosine phosphorylation
that are important for the activation of PLCγ.PLCε also has additional domains related to its activation by Ras, such as the Ras association motifs
(RA) and the Ras guanine nucleotide exchange factor (RasGEF). The bottom panel illustrates how the various PLC isoforms are activated by different
mechanisms. Not included in this figure is the action of PLCζ, which is unusual in that it is activated at fertilization following its injection into the oocyte
(Module 8: Figure mammalian fertilization).

C 2012 Portland Press Limited www.cellsignallingbiology.org