TiBS 17 - DECEMBER 1992

Regulation of phospholipase C by
G proteins
THE ROI.F. OF INOSITOL PHOSPHATES
in hormone-dependent increases in in-
tracellular free calcium ( C a 2) set the
stage for identifying the pivotal role of
phospholipids and phospholipases as
sources and regulators, respectively, of
second messenger molecules. The best-
characterized system remains the regu-
lated hydrolysis of phosphatidylinositol
4,5-bisphosphate [PtdIns(4,5)P2], The
production of two second messengers
from this molecule by the action of
specific phospholipase C (PLC) enzymes
can be stimulated by growth factors
whose receptors are linked to tyrosine
kinase activity, hormones which act
through G protein-linked receptors, the
concentration of intracellular Ca 2 and
other agents of undefined mechanism.
The participation of G proteins in the
regulation of this activity was initially
suggested by specific requirements for
guanine nucleotides for stimulation by
hormones and the more direct effects
of non-hydrolysable guanine nucleo-
tides and aluminium fluoride (AI~, a uni-
versal activator of the heterotrimeric G
proteins), An additional reagent that
implicated a role for G proteins was the
toxin from Bordatella pertussis, which
ADP-ribosylates the cz-subunits of G~
and Go proteins and attenuates their
function. The action of several hor-
mones was abolished by this toxin, but
in most cases, the toxin had little or
only partial effect, This indicated that a
unique G protein (frequently referred to
as Gp) was involved in this latter stimu-
lation (for reviews see Refs 1, 2). This
review focuses on more recent exper-
iments and their impact on our under-
standing of G protein-linked regulation
of phosphatidylinositol-specific phos-
pholipase C (Ptdlns-PLC).
G p r o t e i n s a n d a c t i v a t i o n
The G proteins that mediate regu-
lation of several effector molecules by
hormones constitute a large family of
highly homologous proteins. The pro-
teins are heterotrimers consisting of cz-,
~- and ~subunits. The ~-subunits ap-
pear to be most diverse and have been
traditionally used to define the purified
heterotrimeric proteins, Frequently, the
cz-subunits can also account for the pri-
P. C. Sternweis and A. V. Smrcka are at the
Department of Pharmacology, K5.100,
University of Texas Southwestern Medical
Center, Dallas, TX 75235, USA.
502
Speci fi c phosphol i pase C enzymes can hydroiyse phosphat i dyl i nosi t ol 4,5-
bi sphosphat e i nto t wo products: i nosi t ol 1, 4, 5-t ri sphosphat e, which regu-
lates the release of intracellular calcium stores, and diacylglycerol, which can
st i mul at e protei n ki nase C. A new group of G prot ei ns, the Gq subfamily,
have recently been shown t o medi ate t he regulation of t hi s act i vi t y by a
vari et y of hormones. How do di f f er ent members of t hi s fami l y modul ate
unique phosphol i pase C i sozymes? What i s t he mechani sm of t hi s regu-
l ati on? How mi ght t he Gq subf ami l y act t o modulate ot her i mpor t ant sec-
ond messenger pathways? The t ool s t o answer t hese quest i ons are being
rapi dl y developed.
mary activity of the G protein, Thus,
Gs~ stimulates adenylate cyclase and
transducin ~ (Gt~) activates a cyclic
GMP-dependent phosphodiesterase in
retina,
The G1 proteins were identified as
inhibitory regulators of adenylate cyc-
lase. More recently, the Gi and Go pro-
teins have been implicated in the regu-
lation of several ion channels, The Gt, G1
and Go proteins are substrates for per-
tussis toxin (PTX); attenuation of hor-
mone action by this toxin
implicates the partici-
pation of one or more of
these proteins. Several
new ~-subunits that are
not substrates for PTX
have been recently ident-
ified by either purification
of proteins or isolation of
homologous cDNAs (Zq,
czn_16 ), Several of these
are discussed below. The
G proteins and their func-
tions have been reviewed
extensively (see Refs 3-8
for examples).
A short discussion of
the G protein cycle of acti-
vation is presented here
to facilitate subsequent dis-
cussion. Numerous exper-
iments support a simple
model for the activation
of G proteins (Fig. 1). In
the basal state, the cz-sub-
unit contains bound GDP,
and association of ~-and
137-subunlts is highly
favored, Stimulation of the G protein
results when it binds GTP rather than
GDP. Receptors interact most efficiently
with the heterotrimeric form of the G
protein and accelerate activation by
increasing the rate of dissociation of
GDP and potentially enhancing associ-
ation of GTP. When activated, the affinity
between the ~- and ~7-subunits of the G
protein is decreased, This increases the
likelihood of dissociation of subunits and
the generation of two potential path-
G D P " ~ _ , "
F i g u r e 1
Model for activation of G proteins. The functional state
of a G protein is determined by its bound nucleotide.
With GDP, the G prOtein is inactive and subunit as-
. . . . . . . . . . is favored. With bound GTP, the G protein is
activated and the affinity between its o~- and 13~
subunits is markedly reduced. Receptors stimulate G
pr(~teins by catalysing exchange of GTP for GDP.
1992, Elsevier Science Publishers, (UK)
T I B S 3_7 - DECEMBER 1992
48
57
65
G~ f ami l y
Go f ami l y
G~2 f ami l y
P t d l n s - P L C
~ z
(X,q +
C(,11 4-
0('14 4"
0( 15 ?
C~16 +
( ~12 o
(~13 ' )
F i g u r e 2
Rel at i onshi p among known PTX-insensitive G orotein
(z-subunits. The names and members o f t he subfamilies
f ol l ow t h e assi gnment suggest ed by Simon and col-
leag ues5. Numoers i ndi cat e t h e percentage amino
acid i dent i t y bet ween subuni t s or t h e average identity
among groups. A plus sign i ndi cat es t h a t t h e (z-sub-
uni t has been shown t o act i vat e Ptdlns-PLC (Refs in
t ext ; A. G. Gilman, P. St er nwei s and colleagues, un-
published).
ways [z(GTP) and free [~y-subunitsl for
downstream regulation. Finally, t he G
protein ~-subunit has an intrinsic hy-
drolytic activity that slow137 (rates <10
min-1) converts GTP to GDP and returns
the G protein to its inactive form
W i l l t h e r e a l G~ i d e n t i f y i t s e l f ' / ,
For several years, mystery surrounded
t he nat ure of the G proteins involved in
t he regulation of PLC-mediated hydroly-
sis of Ptdlns(4,5)p2. First, there ap-
peared t o be at least two types of G pro-
teins involved. Pertussis toxin could be
used to completely or partially inhibit
hormone regulation in several systems,
most notably, stimulation by peptides
in hematopoietic cells such as neutro-
phils. This implicated the G o or G~ pro-
teins. While several at t empt s have been
made to regulate directly a phospho-
lipase activity with t hese proteins, suc-
cess has been elusive. A majority of sys-
tems were not inhibited by PTX. This
indicated t hat some as yet unidentified
G protein t hat lacked the consensus
site for modification by this toxin was
involved. The potential list of candi-
dates for this function has blossomed
in the past two years and clear path-
ways for regulation have been delin-
eated. Three laboratories have recently
purified G proteins t hat can stimulate
PLC. A unique preparation of purified G
protein ~-subunits from bovine brain 9
was first identified as being insensitive
to PTX and shown to contain two
polypeptides identical in sequence to
those deduced from two
highly homologous cDNAs,
eCq and ci (Ref. 10). The
preparation was subse-
quently shown to stimu-
late PLC from brain u. At
the same time, a G pro-
tein immunologically re-
lated to cz~ was isolated
from bovine liver based
on its ability to activate a
PLC activity 12. This prep-
aration, which also con-
tains CZqand uu, was used
to demonst rat e G protein
regulation of a ]3, but not
a y or 5 isotype of PtdIns-
PLC 13. A G protein isolated
from t urkey eryt hrocyt es
has also been shown to
stimulate PLC from eryth-
rocytes T M . The absolute
identity of the avian G pro-
tein remains to be deter-
mined, but it is immuno-
logically related to ~qm.
Further experiments have demon-
st rat ed that members of the Gq family
can interact with appropriate receptors
and function as the mediator in stimu-
lation of PtdIns-PLC by hormones. Re-
constitution of purified preparations of
Gq with isolated muscarinic receptors
demonst rat ed t hat M1 muscarinic re-
ceptors were much more efficient acti-
vators of the protein t han M2 recep-
tors ~5. This fits with the linkage of M1
and M2 receptors to PTX-insensitive
and -sensitive pathways, respeCtively.
The participation of Gq and its homol-
ogs in t he regulation of PLC by hor-
mones was demonst rat ed in native
membranes by functional intervention
with an ant i body raised against the car-
boxyl terminus of uq/u. Thus. the stimu-
lation of Ptdlns(4,5)P2 hydrolysis by
both bradykinin and guanine nucleo-
tides in membranes from NG108 cells,
angiotensin II and vasopressin in mem-
branes from rat liver and histamine in
membranes from 1321N1 cells, could be
completely or largely blocked by the
anti-cz~/l~ antibodies T M . Similar antibodies
were used to block stimulation of
GTPase activity by a thromboxane A 2
receptor agonist in platelet mem-
branes 17 and to immunoprecipitate two
G protein cz-subunits t hat were photo-
affinity labeled with a GTP analog in
response to vasopressin T M . These re-
suits indicate t hat the Gq subfamily of G
proteins is responsible for a broad
spectrum of regulation of PtdIns-PLC by
G protein-linked receptors.
The regulation of PLC has also been
examined by expression of wild-type
o-subunits of G proteins or ~-subunits
with mutations t hat cause constitutive
activation. Such experiments have indi-
cated t hat both t he aq- and cz11-subunits
can cause activation of PLC activity
when transiently expressed in COS-7
cells 19. Expression of t he PTX-sensitive
cz o proteins or t he PTX-insenSitive ~z
from the Gi family did not effect regu-
lation of PLC activity. Similar exper-
iments have demonst rat ed t hat two
additional members of the Gq family, ~4
and ~zi6, can also stimulate PLC~ ac-
tivities z0. While the purified proteins
used have been mixtures of ~q-family
subunits, these experiments are pre-
sumably looking at effects of specific
members of the CZqSubfamily. The sub-
families of G proteins t hat contain PTX-
insensitive members, as defined by re-
latedness of CDNA sequences, are
shown in Fig. 2.
P h o s p h o l i p a s e c i r c u i t r y : m u l t i p l i c i t y o r
r e d u n d a n c y ?
Several Ptdlns-PLC enzymes t hat
have a requirement for Ca 2+ have been
described (for reviews see Refs 21-23).
Initially, these were described by
source, size and activities, and labeled
0 to E. Three of these, ~, ~5and 7, were
initially isolated from brain and have
been extensively characterized bio-
chemically and their respective cDNAs
have been isolated. The PLC~I isoform
from brain was first shown to be re-
sponsive to G proteins 11'13. In sub-
sequent experiments, a PLC 7 and PLC~5
from brain were not stimulated under
similar cond itions13. PLC7 has been im-
plicated as the target of regulation of
PLC activity by growth factors 24-27. The
mechanism for regulation of PLC5
remains unknown. Screening of cDNA
libraries by low stringency hybrid-
ization has demonst rat ed t hat multiple
isoforms of each of these subtypes
exist. Classification of the various iso-
forms into subgroups is based largely
on potential general st ruct ure and
homologies as interpreted from cDNA
sequences 28. There have been three
apparent isoforms of PLC~ cDNAs ident-
ified28, 29, This raises several questions.
Are all t hree PLC~ isoforms stimulated
by G proteins, and will t hese responses
be to similar or unique G proteins? Do
the PLC[~ isoforms have similar activi-
ties or are t hey behaviorally unique?
There are potential roles t hat dif-
ferent isoforms of G protein responsive
PtdIns-PLC might fill. One might be to
503
TI BS 1 7 - DECEMBER 1992
$
Figure 3
Putative pathways f or the mechanism of regulation of Ptdlns-PLC by Gq. Evidence for the regulation of thi s activity by either (~- or ~7-subunits
has been presented (see text). The pathway utilized may depend on the subtype of Ptdlns-PLC or the components of the (3 protein. Both
pathways may be active on the same enzyme and the relationship of thi s regulation by both subunits is currently being investigated.
pr ovi de a uni que r e s p o n s e in speci f i c
t i s s ue s or cells. It is pos s i bl e t hat
specific distribution of PLC[~ i sot ypes may
be r el at ed t o t he di s t r i but i on of speci f i c
r egul at or y G pr ot ei ns. Wher eas t he [31
i s of or m is pr e s e nt in a wi de var i et y of
t i s s ue s 21, it is of i nt er es t t hat t he PLC[~2
was cl oned from HL60 cel l s and may be
l i mi t ed in its e xpr e s s i on 28,29. Since t he
cz~6-subunit is l ocal i zed t o cel l s of hema-
t opoi e t i c origin 3, it is pos s i bl e t hat G16
and PLC[32 ar e meant for each ot her.
Anot her pot ent i al r ol e of a PLC[3 i s ot ype
might b e r egul at i on b y t he Go or G~ pro-
t ei ns. Thi s coul d expl ai n PTX-sensitive
r egul at i on of PtdIns-PLC. One c a ve a t t o
t hi s hypot he s i s is t hat initial da t a wi t h
r e s ol ve d PLC~ i s ot ype s i ndi cat e t hat all
t hr e e can b e s t i mul at ed wi t h ~q. There-
fore, one of t h e s e l i pas es woul d have t o
be r e s pons i ve t o bot h PTX-sensitive
and -i nsensi t i ve pat hways .
Are t he r e Ptdlns-PLC e nz yme s ot he r
t han t h e [3-subtypes t hat ar e r egul at ed
b y G pr ot ei ns ? If t he [~ i s ot ype s ar e not
r e s pons i bl e for t he PTX-sensitive pat h-
ways, t he a ns we r has t o be affirmative.
504
Furt her, t he r e is a PtdIns-PLC act i vi t y
r e por t e d from br ai n t hat can b e acti-
vat ed b y permeabilized, GTPyS-activated
HL60 cel l s 31. The act i vi t y r equi r ement s ,
puri fi cat i on profi l e and put at i ve mol-
ecul ar size, do not mat ch t h o s e of char-
act er i zed PLC[3 i s ot ypes . The act i vi t y
ma y refl ect ei t her a uni que s u b c a t e g o r y
of PtdIns-PLC or s ome of t he pr ope r t i e s
mi ght mat ch t h o s e of PLC8 enzymes.
o~ a n d / o r ~(
A l ongst andi ng and f r equent l y con-
t r over s i al que s t i on wi t h G pr ot ei n
pa t hwa ys is whe t he r t he downs t r e a m
-regulation is ef f ect ed b y t he cz- or ~7-
s ubuni t s . The ~-subunits have, for t he
mos t part , domi na t e d t he pi ct ur e. It is
cl ear t hat purified ~-subuni t s al one can
st i mul at e purified adenyl at e cycl as e and
cGMP- dependent phos phodi e s t e r a s e .
Thi s is al so t he c a s e wi t h PLC[31 and CZq
(Ref. 11). Act i vat ed ~q s t i mul at es t he
e nz yme at all t e s t e d c onc e nt r a t i ons of
Ca 2+ and s ubs t r at e 32. The maj or mech-
ani sm for act i vat i on t hen a ppe a r s .tO be
an i ncr eas e in t he a ppa r e nt Vmax of t he
enzyme. When [37-subunits we r e a dde d
t o PLC[31, t h e y had little effect on t he
bas al act i vi t y of t he e nz yme or t he
act i vi t y of t he PLC aft er act i vat i on wi t h
t he GTPyS act i vat ed form of CZq (Ref. 32).
The st i mul at i on of PLC b y ~q, whi ch
was act i vat ed b y A1F~, however , was
mar kedl y i nhi bi t ed b y t he [~y-subunits.
Thi s wa g pr e s uma bl y d u e t o t he re-
ver s al of act i vat i on of t he ~- subuni t by
AI ~ r at her t han a di r ect effect of t he
[37-subunit on t he e nz yme itself.
By cont r as t , a PLC act i vi t y der i ved
from HL60 cel l s is s t i mul at ed b y prep-
ar at i ons of ~7-subunits 33. In t hi s inves-
tigation, t h e aut hor s s e p a r a t e d t wo
f or ms of PtdIns-PLC and de mons t r a t e d
t hat onl y one coul d be s t i mul at ed by 97-
s ubuni t s . This s el ect i vi t y and a var i et y
of ot he r cont r ol s i ndi cat e t hat t he
st i mul at i on is not s i mpl y a non-speci fi c
ef f ect in t h e s e as s ays . Recent l y, we and
ot he r s (P. Gi erschi k and col l eagues,
per s. commun. ) have conf i r med t hi s
n o v e l st i mul at i on of Ptdlns-PLC activi-
t i es b y fiy-suhunits in pr e pa r a t i ons of
puri fi ed PLC[~2 from t he s a me cells.
TI BS 1 7 - DECEMBER 1992
These results indicate t hat some forms
of PtdIns-PLC may be regulated by bot h
a- and [~y-subunits. This would be anal-
ogous to the multiplex regulation of sub-
types of adenylate cyclase 34. While ~s is
required to activate all of the subt ypes
of adenylate cyclase, the [37-subunits
can either potentiate, at t enuat e or have
no effect on this activity depending on
the subt ype of the cyclase. It is of in-
t erest here that t he effect of [3y on
PtdIns-PLC does not appear to require
an a-subunit. It remains to be deter-
mined what the combined effect of bot h
a- and [3~/-subunits might be on respon-
sive enzymes. These potential modes
for regulation of Ptdlns-PLC by subunits
are presented schematically in Fig. 3.
If the [3~/-subunits from the Go and G~
proteins can effect t he activation of
Ptdlns-PLC, this mechanism could pro-
vide the means for PTX-sensitive stimu-
lation of Ptdlns-PLC by hormones. A
caveat to these results is the relatively
high amount of [~y required to provide
stimulation of t he PLC activities (about
1 ~M [3~ as opposed to stimulation by nM
concentrations of czq). One interpret-
ation is t hat the more pot ent a-subunit
is the primary activator. It might be
t hat the aq provides a specific effect by
a less abundant Gq while t he effect of [3y
is derived from more abundant G pro-
teins and is designed for use in concert
with activation of ot her pathways. A
simpler explanation for the relatively
poor pot ency of the [3y-subunits may
just be t hat t he reconstitutions have
not yet been optimized, or experiments
have not used the right [3y. Clearly, regu-
lation by [3y-subunits would be most
optimal if only specific [~/dimers were
effective; this would negate a potential
promiscuous regulation by all G pro-
teins. If indeed, t here is specificity for
[3~/dimers, the rapidly increasing num-
ber of 7-subunits being discovered sug-
gest t hat the specificity may reside in
t hese small polypeptides.
Other directions raise more questions
Wh i l e a s t i mu l a t o r y p a t h wa y can be
established for the generation of inosi-
tol 1,4,5-trisphosphate [Ins(1,4,5)/'3]
and diacylglycerol (bAG), t he impact of
other influences on t he pat hway re-
mains t o be explored. The pat hway can
clearly be down-regulated and this may
be due to bot h desensitization of recep-
tors and apparent effects downst ream
from t he receptor. Phorbol esters, pre-
sumably through the action of protein
kinase C (PKC), can be shown to reduce
hormone responses in cells as well as
Ptdl ns(4, 5 ) P 2
R ~ G q ~ Pt dl ns- PLC I n s ( 1 , 4 , 5 ) P 3 + D A G
R ~ G? - - - - ~ P L - P L C
R ~ G? ~ P L D
PC
P - C h o l i n e + D A G
~----I~ C h o l i n e + P A
PA
P - t a s e
P C
R ~ Go ~ : : P L A 2 C
~ L y s o - P C + A A
Figure 4
Potential pathways for generation of phospholipid-derived second messengers. Several
pathways for the generation of diacylglycerol (DAG), phosphatidic acid (PA), and arachidonic
acid (AA) have been proposed and some evidence for the involvement of G proteins pre-
sented. Only the regulation of Ptdlns-PLC enzymes is clearly established. A potential role
for Gq and i ts homologs in these other pathways or the identification of new G proteins
remains to be determined. PC, phosphatidylcholine.
stimulation in membranes by guanine
nucleotides. Thus, PKC acts as a feed-
back regulator. A potential site for PKC-
mediated phosphorylation is PLC[3 (Ref.
35). While phosphorylation of PLC[31 in
vitro did not affect the activity of the
enzyme, it was postulated t hat the
modification might uncouple the phos-
pholipase from t he regulatory G pro-
tein. So far, concret e evidence for this
t heory has been elusive. Initial studies
have not provided evidence for phos-
phorylation of the Gq proteins, but sev-
eral receptors can be modified by PKC.
The relevance of such events is not
established.
Extracellular stimuli can also cause
inhibition of PLC. Inhibitory effects of
guanine nucleotides on PLC i n mem-
branes or extracts have also been ob-
served 16,36-38. Is this negative regulation
due to G proteins; if so, which ones?
What about the generation of bAG?
While Gq stimulates Ptdlns-PLC, these
enzymes are specific for phosphatidyl-
inositols, especially the phosph0ryl at ed
forms. Yet, in many systems, a large
complement of t he DAG is derived from
other phospholipids in response to hor-
mones. This implies t hat there are
other phospholipases t hat are regu-
lated by G proteins (Fig. 4). Thes e may
include PLC enzymes with wider spec-
trums of phospholipid subst r at es for
direct generation of DAG. An alternative
pat hway is the generation of phospha-
tidic acid by phospholipase D with sub-
sequent generation of bAG through the
action of phosphatidic acid phospha-
tase. Phosphatidic acid itself has been
proposed to be a second messenger.
Finally, G proteins have been impli-
cated in the generation of arachidonic
acid and its metabolites. This may be
through a direct action on a non-se-
cretory phospholipase A2 or by more in-
direct pathways. It is possible t hat fam-
ilies of enzymes exist for these activities
in analogy to the PtdIns-PLC family and
t hat at least one i sot ype in each family
is regulated by G proteins (Fig. 4). If so,
will the G proteins be from the Gq sub-
family or some new family yet to be
described? The stimulation of multiple
activities by the same hormone in some
cells might suggest a common G protein
pathway. The development of specific
antibodies for G protein ~-subunits t hat
can block their action should allow the
resolution of some of t hese questions.
Summary
A subclass of G proteins ( Gq) has
been described and shown to regulate
Ptdlns-specific PLC of t he 13 subtype.
The a-subunits of several G proteins in
this class have been shown to have this
activity, although the efficacy of each
with respect to different phospholipases
remai ns to be determined. Similarly,
several phospholipase [~ isotype en-
zymes appear to respond to G proteins.
505
While there are indications that some
other non-J3 PLC enzymes interact with
G proteins, their identities need to be
determined. The observations that [37-
subunits can regulate some forms of
PLC raise questions about the specificity
of PLC stimulation but also offer a puta-
tive pathway for PTX-sensitive stimu-
lation of this signalling pathway. Finally,
the emergence of the Gq proteins as regu-
lators of Ptdlns-PLC invite the specu-
lation that they may participate in hor-
monal regulation of other lipid-derived
second messengers. The tools are at
hand to dramatically improve our
understanding of this intricate network
for regulation of these important sec-
ond messengers.
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DESCRIPTIONS OF SEVERAL regulatory
phenomena that are responsible for
short-term adaptations by microbes
have hitherto been based on physio-
logical observations; however, increased
knowledge of the underlying biochemi-
cal and genetic mechanisms now means
that the terms used can be defined
quite rigorously to remove the confusion
that exists surrounding nomenclature.
Ambiguities in the nomenclature of
regulatory mechanisms stem partly
from applying some expressions, already
used for physiological changes, to
molecular events. For example, either
one or both of the two different physio-
logical controls, 'induction' and 'de-
repression', may regulate the synthesis
of enzymes involved in utilizing a given
substrate. However, in molecular terms,
induction inactivates a repressor, so
induction and derepression may seem
to be the same phenomenon. The ex-
tensive studies that have been published
K-D1 Ent i an i s at t he I nst i t ut f or M~krobi ol ogi e
der Johann Wol f gang Goet he-Uni versi t &t
Frankfurt, Theodor-St ern-Kai 7, Haus 75A,
D- 6000 Fr a n k f u r t / M, Germany. J. A. Barnett
i s at t he School of Bi ol ogi cal Sci ences,
Uni versi t y of East Angi i a, Norwi ch,
UK NR4 7TJ.
5O6
There ar e several kinds of regulation t h a t enabl e microbes t o cope with
rapidly changing suppl i es of nutrients. This is exemplified by sugar metab-
olism in Saccharomyces cerevisiae. Some readily reversible controls
a f f e c t t he activity of enzymes, ei t her by allosteric activation and deacti-
vation, whi ch often occur within seconds, or by covalent modification, with-
in mi nut es. Ot her controls regulate t he amount of enzyme pr esent in t he
cel l s, ei t her by irreversible proteolytic inactivation of t he enzyme, or by
influencing enzymic synthesis. The nomenclature of t h e s e pr ocesses is
often confused.
on sugar metabolism by the yeast, Sac-
charomyces cerevisiae, now make it poss-
ible to integrate many physiological and
genetic findings more precisely than
before, allowing the clarification of the
nomenclature and the regulatory pro-
cesses themselves.
The utilization of sugars by yeasts is
regulated by several kinds of enzymic
control, described in physiological terms
as allosteric activation and dea~:ti-
vation, interconversion, specific proteol-
ysis (inactivation) and induction, re-
pression and derepression. Allosteric
activation, deactivation and intercon-
version refer to the regulation of the
activities of enzymes; whereas inacti-
vation, induction, repression and de-
repression are mechanisms by which
the amount of enzyme is regulated.
Like other yeasts, S. cerevisiae grows
on hexose sugars, such as glucose,
1992, Elsevier Science Publishers, (UK)