CHAPTER 2Overview of Cellular Physiology in Medical Physiology 55
is activated by heterotrimeric G proteins, while PLCγ forms are
activated through tyrosine kinase receptors. PLC isoforms can
catalyze the hydrolysis of the membrane lipid phosphatidyl-
inositol 4,5-diphosphate (PIP 2 ) to form IP 3 and diacylglycerol
(DAG) (Figure 2–25). The IP 3 diffuses to the endoplasmic
reticulum, where it triggers the release of Ca2+ into the cyto-
plasm by binding the IP 3 receptor, a ligand-gated Ca2+ chan-
nel (Figure 2–26). DAG is also a second messenger; it stays in
the cell membrane, where it activates one of several isoforms
of protein kinase C.
FIGURE 2–24 Structures of two G protein-coupled receptors. The individual amino acid residues are identified by their single-letter codes,
and the orange residues are sites of phosphorylation. The Y-shaped symbols identify glycosylation sites. Note the extracellular amino terminal, the
intracellular carboxyl terminal, and the seven membrane-spanning portions of each protein. (Reproduced with permission from Benovic JL et al: Light-
dependent phosphorylation of rhodopsin by β-adrenergic receptor kinase. Reprinted by permission from Nature 1986;321:869. Copyright © 1986 by Macmillan Magazines)
HDPVHSGNTTLLFDSDNGPPGM
VD
TE
ER
DE
WA
VV
IGLMMAS
VIV
VFLGVNI
TAI
LAIV
BLAIGNF
PVV
AVCLADL
STI
ALGM
NH 2
AK
F
MW
NFGN
FW
KM C
ERLQTVTN
FY
TESFIWD
VLC
LICEVTI
AVD
VTAS
AR
HT
KQ
AI
DCYHKET
CC
DF
FT
YWH N
MLQFISP
VVMILWI
VMR
TLQS
RY
IA
TI
SPF
KYQS
LL
KT
KN
A
AQIAAYS
SIV
VPMLVVF
VYSL
SFYV
RV
FQV
AKRQ
GQVEQDGRSG
LQKI
ESKD
RR
SS
KLCFK
AKHE
KL
T
HGL
PSHFRG
NL
QDN
LIP
IVH K
VIIFNFV
TLGTMFI
IG
PLWC
SPD
FRIAFQ
EL
LC
LR
R
IELVLYN
WLG
PALFINY
CR
YVNS
GY S
S
EGMYDTKGNGNSSYGN AKS
QEKESERL
GSA
CQ
LG TESFVNCQ
G
EDPPG
QSDLSLSPVT
C
HOOCLPSDNTSCNRG
2 -Adrenergic receptor
Extracellular
surface
Cytoplasmic
surface
PSRVVCTKNSFPVYFNPGETG
EF
AP
QY
YL
AE
PW
QFSM
LMAFALY
IGNFFPL
TLY
LIML
TTTYTLF
QGF
ADLANVL
LIY
VMFL
NMNH 2
VT
V
GH
F
FY
V
GP
LE
GC
T
N
LS G
QHKKLRTP
NL
LFGAGTE
IAL
IVELRAY
VVV
WSLA
RS
IY
QM
C
EP
G
SCGIDY
YT
PH
EE
TN
WGV N
LAPCPAA
AWVTGFM
IAH
LAMV
CK
PMSNFRFG
NE
VEISYFM
FVV
VPILFIF
CYG M
HFII
QL
VF
TV
KEAAAQQQE T
T
SA
KEAKQ
TVE
R
T
HQGSDF
GP
FFAIVYQ
AYP
ILVFMAI
IV
LWCI
MN
KQFRNCM
VT
TL
CC
G
TIIFPMA
FFA
PVVYINY
IM
KTSA
HOOCAPAVQSTETKSVTTSAEDDGLPNK
Intradiskal Rhodopsin
surface
Cytoplasmic surface
F
FIGURE 2–25 Metabolism of phosphatidylinositol in cell membranes. Phosphatidylinositol is successively phosphorylated to form
phosphatidylinositol 4-phosphate (PIP), then phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Phospholipase Cβ and phospholipase Cγ catalyze the
breakdown of PIP 2 to inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol. Other inositol phosphates and phosphatidylinositol derivatives can also
be formed. IP 3 is dephosphorylated to inositol, and diacylglycerol is metabolized to cytosine diphosphate (CDP)-diacylglycerol. CDP-diacylglycerol
and inositol then combine to form phosphatidylinositol, completing the cycle. (Modified from Berridge MJ: Inositol triphosphate and diacylglycerol as second
messengers. Biochem J 1984;220:345.)
P
1
4
P
P
1
4
P
P P
1
4 5
5
P
P P
1
4
Phosphatidylinositol
(PI)
PIP PIP 2 Diacylglycerol
IP 2
IP 3
Phospholipase
C
Inositol IP
CDP-diacylglycerol Phosphatidic acid
+