![The emerging roles of phosphatases in Hedgehog pathway...ture, stability, activity, protein-protein interaction [6]. In contrast to protein kinases, protein phosphatases have been](https://static.fdocuments.in/doc/165x107/60ee63efe2bdd8639d7712a6/the-emerging-roles-of-phosphatases-in-hedgehog-pathway-ture-stability-activity.jpg)
SnapShot: Lipid Kinases and Phosphatases
2
1654 Cell 155, December 19, 2013 ©2013 Elsevier Inc. DOI http://dx.doi.org/10.1016/j.cell.2013.12.005 See online version for legend and references. SnapShot: Lipid Kinases and Phosphatases Simon A. Rudge and Michael J. O. Wakelam The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK Gene Reaction(s) catalyzed in vitro Reaction(s) catalyzed in vivo PIK3C3 PI → PI(3)P PI → PI(3)P PIK3C2A PI → PI(3)P, PI(4)P → PI(3,4)P 2 , PI(4,5)P 2 → PI(3,4,5)P 3 PI → PI(3)P, PI(4)P → PI(3,4)P 2 PIK3C2B PI → PI(3)P, PI(4)P → PI(3,4)P 2 , PI(4,5)P 2 → PI(3,4,5)P 3 PI → PI(3)P PIK3C2G PI → PI(3)P, PI(4)P → PI(3,4)P 2 _ PIKFYVE PI → PI(5)P, PI(3)P → PI(3,5)P 2 PI → PI(5)P, PI(3)P → PI(3,5)P 2 PIP4K2A PI(3)P → PI(3,4)P 2 → PI(3,4,5)P 3 , PI(5)P → PI(4,5)P 2 PI(5)P → PI(4,5)P 2 PIP4K2B PI(3)P → PI(3,4)P 2 , PI(5)P → PI(4,5)P 2 PI(5)P → PI(4,5)P 2 PIP4K2C PI(5)P → PI(4,5)P 2 _ PIK3CA PI → PI(3)P, PI(4)P → PI(3,4)P 2 , PI(4,5)P 2 → PI(3,4,5)P 3 PI(4,5)P 2 → PI(3,4,5)P 3 PIK3CB PI → PI(3)P, PI(4)P → PI(3,4)P 2 , PI(4,5)P 2 → PI(3,4,5)P 3 PI(4,5)P 2 → PI(3,4,5)P 3 PIK3CD PI → PI(3)P, PI(4)P → PI(3,4)P 2 , PI(4,5)P 2 → PI(3,4,5)P 3 PI(4,5)P 2 → PI(3,4,5)P 3 PIK3CG PI → PI(3)P, PI(4)P → PI(3,4)P 2 , PI(4,5)P 2 → PI(3,4,5)P 3 PI(4,5)P 2 → PI(3,4,5)P 3 IPMK PI(4,5)P 2 → PI(3,4,5)P 3 PI(4,5)P 2 → PI(3,4,5)P 3 PIP5K1A PI → PI(5)P, PI(3)P → PI(3,4)P 2 → PI(3,4,5)P 3 , PI(3)P → PI(3,5)P 2 , PI(4)P → PI(4,5)P 2 , PI(3,4)P 2 → PI(3,4,5)P 3 PI(4)P → PI(4,5)P 2 PIP5K1B PI → PI(5)P, PI(3)P → PI(3,4)P 2 → PI(3,4,5)P 3 , PI(3)P → PI(3,5)P 2 , PI(4)P → PI(4,5)P 2 , PI(3,4)P 2 → PI(3,4,5)P 3 PI(4)P → PI(4,5)P 2 PIP5K1C PI(3)P → PI(3,4)P 2 → PI(3,4,5)P 3 , PI(3)P → PI(3,5)P 2 , PI(4)P → PI(4,5)P 2 , PI(3,4)P 2 → PI(3,4,5)P 3 PI(4)P → PI(4,5)P 2 PI4K2A PI → PI(4)P PI → PI(4)P PI4K2B PI → PI(4)P PI → PI(4)P PI4KA PI → PI(4)P PI → PI(4)P PI4KB PI → PI(4)P PI → PI(4)P MTM1 PI(3)P → PI, PI(3,5)P 2 → PI(5)P PI(3)P → PI, PI(3,5)P 2 → PI(5)P MTMR1 PI(3)P → PI, PI(3,5)P 2 → PI(5)P _ MTMR2 PI(3)P → PI, PI(3,5)P 2 → PI(5)P PI(3)P → PI MTMR3 PI(3)P → PI, PI(3,5)P 2 → PI(5)P PI(3,5)P 2 → PI(5)P MTMR4 PI(3)P → PI PI(3)P → PI MTMR6 PI(3)P → PI, PI(3,5)P 2 → PI(5)P PI(3,5)P 2 → PI(5)P MTMR7 PI(3)P → PI _ MTMR8 PI(3)P → PI, PI(3,5)P 2 → PI(5)P PI(3)P → PI MTMR14 PI(3)P → PI, PI(3,5)P 2 → PI(5)P PI(3)P → PI, PI(3,5)P 2 → PI(5)P PTEN PI(3)P → PI, PI(3,4)P 2 → PI(4)P, PI(3,5)P 2 → PI(5)P, PI(3,4,5)P 3 → PI(4,5)P 2 PI(3,4,5)P 3 → PI(4,5)P 2 TPTE2 PI(3)P → PI, PI(3,4)P 2 → PI(4)P, PI(3,5)P 2 → PI(5)P, PI(3,4,5)P 3 → PI(4,5)P 2 PI(4,5)P 2 → PI(4)P, PI(3,4)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 TMEM55A PI(4,5)P 2 → PI(5)P _ TMEM55B PI(4,5)P 2 → PI(5)P PI(4,5)P 2 → PI(5)P INPP4A PI(3,4)P 2 → PI(3)P PI(3,4)P 2 → PI(3)P INPP4B PI(3,4)P 2 → PI(3)P, PI(3,4,5)P 3 → PI(3,5)P 2 PI(3,4)P 2 → PI(3)P Gene Reaction(s) catalyzed in vitro Reaction(s) catalyzed in vivo PTPMT1 PI(5)P → PI Phosphatidylglycerophosphate → Phosphatidylglycerol FIG4 PI(3,5)P 2 → PI(3)P, PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(3,5)P 2 → PI(3)P OCRL PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(4,5)P 2 → PI(4)P INPP5B PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(4,5)P 2 → PI(4)P INPP5D PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(3,4,5)P 3 → PI(3,4)P 2 INPP5E PI(3,5)P 2 → PI(3)P, PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 INPP5F PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(3,4,5)P 3 → PI(3,4)P 2 INPP5J PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(3,4,5)P 3 → PI(3,4)P 2 INPP5K PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(3,4,5)P 3 → PI(3,4)P 2 INPPL1 PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 PI(4,5)P 2 → PI(4)P, PI(3,4,5)P 3 → PI(3,4)P 2 SACM1L PI(3)P → PI, PI(4)P → PI PI(4)P → PI SYNJ1 PI(3)P → PI, PI(4)P → PI, PI(4,5)P 2 → PI(4)P PI(4,5)P 2 → PI(4)P SYNJ2 PI(4,5)P 2 → PI(4)P _ DGKA DAG → PA DAG → PA DGKB DAG → PA DAG → PA DGKG DAG → PA DAG → PA DGKD DAG → PA DAG → PA DGKE DAG → PA DAG → PA DGKZ DAG → PA DAG → PA DGKH DAG → PA DAG → PA DGKQ DAG → PA DAG →PA DGKI DAG → PA DAG → PA DGKK DAG → PA DAG → PA EIF2AK3 DAG → PA DAG → PA AGK DAG → PA, MAG → LPA DAG → PA , MAG → LPA SPHK1 Sphingosine → Sphingosine 1-phosphate Sphingosine → Sphingosine 1-phosphate SPHK2 Sphingosine → Sphingosine 1-phosphate Sphingosine → Sphingosine 1-phosphate CERK Ceramide → Ceramide 1-phosphate Ceramide → Ceramide 1-phosphate PPAP2A PA → DAG, LPA → MAG, Ceramide 1-phosphate → Ceramide, Sphingosine 1-phosphate → Sphingosine PA → DAG, LPA → MAG, Ceramide 1-phosphate → Ceramide, Sphingosine 1-phosphate → Sphingosine PPAP2B PA → DAG, LPA → MAG, Ceramide 1-phosphate → Ceramide, Sphingosine 1-phosphate → Sphingosine PA → DAG, LPA → MAG, Sphingosine 1-phosphate → Sphingosine PPAP2C PA → DAG, LPA → MAG, Ceramide 1-phosphate → Ceramide, Sphingosine 1-phosphate → Sphingosine PA → DAG, LPA → MAG, Sphingosine 1-phosphate → Sphingosine PPAPDC1A PA → DAG, LPA → MAG, DGPP → PA _ PPAPDC1B PA → DAG, LPA → MAG, DGPP → PA _ PPAPDC2 PSDP → PSMP, FDP → FMP, PA → DAG PSDP → PSMP LPIN1 PA → DAG PA → DAG LPIN2 PA → DAG PA → DAG LPIN3 PA → DAG _ SGPP1 Sphingosine 1-phosphate → Sphingosine Sphingosine 1-phosphate → Sphingosine
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Transcript of SnapShot: Lipid Kinases and Phosphatases
Snap
Shot:
Lip
id K
inas
es
and P
hosp
hat
ases
Sim
on
A. R
udg
e an
d M
icha
el J
. O. W
akel
amT
he B
abra
ham
Inst
itute
, Bab
raha
m R
esea
rch
Cam
pus
, Cam
bri
dg
e C
B22
3AT
, UK
Gen
eR
eact
ion(
s) c
atal
yzed
in v
itro
Rea
ctio
n(s)
cat
alyz
ed in
viv
o
PIK
3C3
PI →
PI(3
)PP
I → P
I(3)P
PIK
3C2A
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2,
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2
PIK
3C2B
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2,
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PI →
PI(3
)P
PIK
3C2G
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2
_
PIK
FYV
EP
I → P
I(5)P
, PI(3
)P →
PI(3
,5)P
2P
I → P
I(5)P
, PI(3
)P →
PI(3
,5)P
2
PIP
4K2A
PI(3
)P →
PI(3
,4)P
2 →
PI(3
,4,5
)P3,
PI(5
)P →
PI(4
,5)P
2P
I(5)P
→ P
I(4,5
)P2
PIP
4K2B
PI(3
)P →
PI(3
,4)P
2, P
I(5)P
→ P
I(4,5
)P2
PI(5
)P →
PI(4
,5)P
2
PIP
4K2C
PI(5
)P →
PI(4
,5)P
2_
PIK
3CA
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2,
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PIK
3CB
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2,
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PIK
3CD
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2,
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PIK
3CG
PI →
PI(3
)P, P
I(4)P
→ P
I(3,4
)P2,
PI(4
,5)P
2 →
PI(3
,4,5
)P3
PI(4
,5)P
2 →
PI(3
,4,5
)P3
IPM
KP
I(4,5
)P2
→ P
I(3,4
,5)P
3P
I(4,5
)P2
→ P
I(3,4
,5)P
3
PIP
5K1A
PI →
PI(5
)P, P
I(3)P
→ P
I(3,4
)P2
→ P
I(3,4
,5)P
3, P
I(3)P
→
PI(3
,5)P
2, P
I(4)P
→ P
I(4,5
)P2,
PI(3
,4)P
2 →
PI(3
,4,5
)P3
PI(4
)P →
PI(4
,5)P
2
PIP
5K1B
PI →
PI(5
)P, P
I(3)P
→ P
I(3,4
)P2
→ P
I(3,4
,5)P
3, P
I(3)P
→
PI(3
,5)P
2, P
I(4)P
→ P
I(4,5
)P2,
PI(3
,4)P
2 →
PI(3
,4,5
)P3
PI(4
)P →
PI(4
,5)P
2
PIP
5K1C
PI(3
)P →
PI(3
,4)P
2 →
PI(3
,4,5
)P3,
PI(3
)P →
PI(3
,5)P
2,
PI(4
)P →
PI(4
,5)P
2, P
I(3,4
)P2
→ P
I(3,4
,5)P
3
PI(4
)P →
PI(4
,5)P
2
PI4
K2A
PI →
PI(4
)PP
I → P
I(4)P
PI4
K2B
PI →
PI(4
)PP
I → P
I(4)P
PI4
KA
PI →
PI(4
)PP
I → P
I(4)P
PI4
KB
PI →
PI(4
)PP
I → P
I(4)P
MTM
1P
I(3)P
→ P
I, P
I(3,5
)P2 →
PI(5
)PP
I(3)P
→ P
I, P
I(3,5
)P2 →
PI(5
)P
MTM
R1
PI(3
)P →
PI,
PI(3
,5)P
2 →
PI(5
)P_
MTM
R2
PI(3
)P →
PI,
PI(3
,5)P
2 →
PI(5
)PP
I(3)P
→ P
I
MTM
R3
PI(3
)P →
PI,
PI(3
,5)P
2 →
PI(5
)PP
I(3,5
)P2 →
PI(5
)P
MTM
R4
PI(3
)P →
PI
PI(3
)P →
PI
MTM
R6
PI(3
)P →
PI,
PI(3
,5)P
2 →
PI(5
)PP
I(3,5
)P2 →
PI(5
)P
MTM
R7
PI(3
)P →
PI
_
MTM
R8
PI(3
)P →
PI,
PI(3
,5)P
2 →
PI(5
)PP
I(3)P
→ P
I
MTM
R14
PI(3
)P →
PI,
PI(3
,5)P
2 →
PI(5
)PP
I(3)P
→ P
I, P
I(3,5
)P2 →
PI(5
)P
PTE
NP
I(3)P
→ P
I, P
I(3,4
)P2
→ P
I(4)P
, PI(3
,5)P
2 →
PI(5
)P,
PI(3
,4,5
)P3 →
PI(4
,5)P
2
PI(3
,4,5
)P3 →
PI(4
,5)P
2
TPTE
2P
I(3)P
→ P
I, P
I(3,4
)P2
→ P
I(4)P
, PI(3
,5)P
2 →
PI(5
)P,
PI(3
,4,5
)P3 →
PI(4
,5)P
2
PI(4
,5)P
2 →
PI(4
)P, P
I(3,4
)P2
→ P
I(4)P
, P
I(3,4
,5)P
3 →
PI(3
,4)P
2
TME
M55
AP
I(4,5
)P2
→ P
I(5)P
_
TME
M55
BP
I(4,5
)P2
→ P
I(5)P
PI(4
,5)P
2 →
PI(5
)P
INP
P4A
PI(3
,4)P
2 →
PI(3
)PP
I(3,4
)P2
→ P
I(3)P
INP
P4B
PI(3
,4)P
2 →
PI(3
)P, P
I(3,4
,5)P
3 →
PI(3
,5)P
2P
I(3,4
)P2
→ P
I(3)P
Gen
eR
eact
ion(
s) c
atal
yzed
in v
itro
Rea
ctio
n(s)
cat
alyz
ed in
viv
o
PTP
MT1
PI(5
)P →
PI
Pho
spha
tidyl
glyc
erop
hosp
hate
→
Pho
spha
tidyl
glyc
erol
FIG
4P
I(3,5
)P2
→ P
I(3)P
, PI(4
,5)P
2 →
PI(4
)P, P
I(3,4
,5)P
3 →
P
I(3,4
)P2
PI(3
,5)P
2 →
PI(3
)P
OC
RL
PI(4
,5)P
2 →
PI(4
)P, P
I(3,4
,5)P
3 →
PI(3
,4)P
2P
I(4,5
)P2
→ P
I(4)P
INP
P5B
PI(4
,5)P
2 →
PI(4
)P, P
I(3,4
,5)P
3 →
PI(3
,4)P
2P
I(4,5
)P2
→ P
I(4)P
INP
P5D
P
I(4,5
)P2
→ P
I(4)P
, PI(3
,4,5
)P3
→ P
I(3,4
)P2
PI(3
,4,5
)P3
→ P
I(3,4
)P2
INP
P5E
PI(3
,5)P
2 →
PI(3
)P, P
I(4,5
)P2
→ P
I(4)P
, PI(3
,4,5
)P3
→
PI(3
,4)P
2
PI(4
,5)P
2 →
PI(4
)P, P
I(3,4
,5)P
3 →
PI(3
,4)P
2
INP
P5F
P
I(4,5
)P2
→ P
I(4)P
, PI(3
,4,5
)P3 →
PI(3
,4)P
2P
I(3,4
,5)P
3 →
PI(3
,4)P
2
INP
P5J
PI(4
,5)P
2 →
PI(4
)P, P
I(3,4
,5)P
3 →
PI(3
,4)P
2P
I(3,4
,5)P
3 →
PI(3
,4)P
2
INP
P5K
P
I(4,5
)P2
→ P
I(4)P
, PI(3
,4,5
)P3
→ P
I(3,4
)P2
PI(3
,4,5
)P3
→ P
I(3,4
)P2
INP
PL1
PI(4
,5)P
2 →
PI(4
)P, P
I(3,4
,5)P
3 →
PI(3
,4)P
2P
I(4,5
)P2
→ P
I(4)P
, PI(3
,4,5
)P3
→ P
I(3,4
)P2
SA
CM
1LP
I(3)P
→ P
I, P
I(4)P
→ P
IP
I(4)P
→ P
I
SY
NJ1
PI(3
)P →
PI,
PI(4
)P →
PI,
PI(4
,5)P
2 →
PI(4
)PP
I(4,5
)P2
→ P
I(4)P
SY
NJ2
PI(4
,5)P
2 →
PI(4
)P_
DG
KA
DA
G →
PA
DA
G →
PA
DG
KB
DA
G →
PA
DA
G →
PA
DG
KG
DA
G →
PA
DA
G →
PA
DG
KD
DA
G →
PA
DA
G →
PA
DG
KE
DA
G →
PA
DA
G →
PA
DG
KZ
DA
G →
PA
DA
G →
PA
DG
KH
DA
G →
PA
DA
G →
PA
DG
KQ
DA
G →
PA
DA
G →
PA
DG
KI
DA
G →
PA
DA
G →
PA
DG
KK
DA
G →
PA
DA
G →
PA
EIF
2AK
3D
AG
→ P
AD
AG
→ P
A
AG
KD
AG
→ P
A, M
AG
→ L
PAD
AG
→ P
A ,
MA
G →
LPA
SP
HK
1S
phi
ngos
ine
→ S
phi
ngos
ine
1-p
hosp
hate
Sp
hing
osin
e →
Sp
hing
osin
e 1-
pho
spha
te
SP
HK
2S
phi
ngos
ine
→ S
phi
ngos
ine
1-p
hosp
hate
Sp
hing
osin
e →
Sp
hing
osin
e 1-
pho
spha
te
CE
RK
Cer
amid
e →
Cer
amid
e 1-
pho
spha
teC
eram
ide
→ C
eram
ide
1-p
hosp
hate
PPA
P2A
PA →
DA
G, L
PA →
MA
G, C
eram
ide
1-p
hosp
hate
→
Cer
amid
e, S
phi
ngos
ine
1-p
hosp
hate
→ S
phi
ngos
ine
PA →
DA
G, L
PA →
MA
G, C
eram
ide
1-p
hosp
hate
→ C
eram
ide,
Sp
hing
osin
e 1-
pho
spha
te →
Sp
hing
osin
e
PPA
P2B
PA →
DA
G, L
PA →
MA
G, C
eram
ide
1-p
hosp
hate
→
Cer
amid
e, S
phi
ngos
ine
1-p
hosp
hate
→ S
phi
ngos
ine
PA →
DA
G, L
PA →
MA
G, S
phi
ngos
ine
1-p
hosp
hate
→ S
phi
ngos
ine
PPA
P2C
PA →
DA
G, L
PA →
MA
G, C
eram
ide
1-p
hosp
hate
→
Cer
amid
e, S
phi
ngos
ine
1-p
hosp
hate
→ S
phi
ngos
ine
PA →
DA
G, L
PA →
MA
G, S
phi
ngos
ine
1-p
hosp
hate
→ S
phi
ngos
ine
PPA
PD
C1A
PA →
DA
G, L
PA →
MA
G, D
GP
P →
PA
_
PPA
PD
C1B
PA →
DA
G, L
PA →
MA
G, D
GP
P →
PA
_
PPA
PD
C2
PS
DP
→ P
SM
P, F
DP
→ F
MP,
PA
→ D
AG
PS
DP
→ P
SM
P
LPIN
1PA
→ D
AG
PA →
DA
G
LPIN
2PA
→ D
AG
PA →
DA
G
LPIN
3PA
→ D
AG
_
SG
PP
1S
phi
ngos
ine
1-p
hosp
hate
→ S
phi
ngos
ine
Sp
hing
osin
e 1-
pho
spha
te →
Sp
hing
osin
e
1654 Cell 155, December 19, 2013 ©2013 Elsevier Inc. DOI http://dx.doi.org/10.1016/j.cell.2013.12.005 See online version for legend and references.
SnapShot: Lipid Kinases and PhosphatasesSimon A. Rudge and Michael J. O. WakelamThe Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK
This SnapShot presents the mammalian proteins that have been identified as enzymes that catalyze the phosphorylation or dephosphorylation of lipid substrates. We have included both the in vitro and in vivo reactions reported in the literature to highlight the importance of assessing the data from both sources.
We have limited the results from in vitro experiments to those published using full-length native or recombinant proteins; consequently, we have not included those reactions catalyzed by nonregulated, isolated catalytic domains. For the in vivo data, in addition to reports in which accurate measurements of the lipid substrates and products have been performed in cells, we have included the reactions identified using indirect measurements made using fluorescently tagged proteins expressed in cells that bind specifi-cally to the lipid substrate and/or product in question.
The differences between the in vitro and in vivo reactions catalyzed by some lipid kinases and phosphatases further illustrates the importance of in vivo validation of enzyme reactions measured in the test tube.
Several reasons could explain differences in substrate specificity of a lipid kinase or phosphatase measured in a living cell or animal, compared to a test tube assay: (1) the cellular localization of the enzyme and, consequently, the access that the kinase or phosphatase has to its lipid substrate; (2) the unique membrane and protein environment in which the lipid substrate is presented to the enzyme; and (3) the presence of regulatory proteins and lipids in the cell that could determine which lipid substrates are engaged in vivo but that could be absent from an in vitro assay.
Furthermore, the technical challenges associated with accurately measuring the products of lipid kinase and phosphatase reactions in vivo could also contribute and, in some cases, could explain why similar in vivo data has not been reported.
Phospholipids are made up of different fatty acid moieties at the sn1 and sn2 position of the glycerol backbone and indeed can have acyl, alkyl, or alkenyl linkages; thus, for any given phospholipid, multiple molecular species exist that differ in the length and saturation of the fatty acid moieties. New methodologies in mass spectrometry are now revealing that the products of lipid kinase reactions measurable in vivo, such as PI(3,4,5)P3, are limited to only a few molecular species, suggesting that the kinases and phosphatases that are responsible for PI(3,4,5)P3 metabolism are selective for different molecular species.
Although this SnapShot has focused on the phosphatases that antagonize the actions of the lipid kinases, the products of the kinase reactions can in some cases be degraded by alternative activities. For example, sphingosine-1-phosphate can be degraded by a lysase activity. Furthermore, PI(4,5)P2 and PA can be metabolized by phos-pholipase enzymes: phosphoinositide-specific phospholipase C hydrolyses PI(4,5)P2 to generate DAG and inositol (1,4,5)P3, and phospholipase A1 and A2 hydrolyse PA to generate LPA.
ABBREVIATIONS
PI, phosphatidylinositol; PI(3)P, phosphatidylinositol 3-phosphate; PI(4)P, phosphatidylinositol 4-phosphate; PI(5)P, phosphatidylinositol 5-phosphate; PI(3,4)P2, phosphatidylino-sitol 3,4-bisphosphate; PI(3,5)P2, phosphatidylinositol 3,5-bisphosphate; PI(4,5)P2, phosphatidylinositol 4,5-bisphosphate; PI(3,4,5)P3, phosphatidylinositol 3,4,5-trisphosphate; PA, phosphatidic acid; LPA, lyso-phosphatidic acid; DAG, diacylglycerol; MAG, monoacylglycerol; DGPP, diacylglycerol pyrophosphate; PSDP, presqualine diphosphate; PSMP, presqualine monophosphate; FDP, farnesyl diphosphate; FMP, farnesyl monophosphate.
AckNOwlEdGmENTS
Work in the S.A.R. and M.J.O.W. lab is supported by the Biotechnology and Biological Sciences Research Council.
REfERENcES
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1654.e1 Cell 155, December 19, 2013 ©2013 Elsevier Inc. DOI http://dx.doi.org/10.1016/j.cell.2013.12.005
