PMID- 10487978
OWN - NLM
STAT- MEDLINE
DCOM- 19990922
LR  - 20190831
IS  - 1093-9946 (Print)
IS  - 1093-4715 (Linking)
VI  - 4
DP  - 1999 Sep 15
TI  - Phosphorylase kinase: the complexity of its regulation is reflected in the
      complexity of its structure.
PG  - D618-41
AB  - Intracellular glycogen stores are used to maintain blood-glucose homeostasis
      during fasting, are a source of energy for muscle contraction, and are used to
      support a broad range of cellular activities in most tissues. A diversity of
      signals accelerate glycogen degradation that are mediated by phosphorylase b
      kinase (Phk), which phosphorylates and thereby activates glycogen phosphorylase. 
      Phk is among the most complex of the protein kinases so far elucidated. It has
      one catalytic (gamma) subunit and three different regulatory (alpha, beta, and
      delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme
      molecule is presumed to contain four molecules of each subunit. The three
      regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.
      Ca2+ relieves inhibition via the delta subunit, which is identical to calmodulin 
      but remains an integral component of the holoenzyme even when the [Ca2+] is
      lowered to nanomolar levels. Phosphorylation of the alpha and beta subunits by
      the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)
      also relieves inhibition of the gamma subunit and thereby activates the enzyme.
      The stimulatory effects of Ca2+ and phosphorylation appear to be structurally
      coupled and are cooperative. In addition, Phk is activated in vitro by
      autophosphorylation, limited proteolysis of the regulatory subunits, and various 
      allosteric effectors and these may also be mechanisms of physiological
      importance. The molecular mechanisms of regulation are currently poorly
      understood, but new insights are beginning to emerge. This review discusses
      current knowledge and concepts of the structure, function and regulation of Phk.
FAU - Brushia, R J
AU  - Brushia RJ
AD  - Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Rd.,
      MS1-260, Berkeley, CA 94720, USA.
FAU - Walsh, D A
AU  - Walsh DA
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 19990915
PL  - United States
TA  - Front Biosci
JT  - Frontiers in bioscience : a journal and virtual library
JID - 9709506
RN  - 0 (Holoenzymes)
RN  - 0 (Isoenzymes)
RN  - EC 2.7.1.19 (Phosphorylase Kinase)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium/physiology
MH  - Consensus Sequence
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Enzyme Activation
MH  - Holoenzymes/chemistry/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Isoenzymes/metabolism
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphorylase Kinase/*chemistry/genetics/*metabolism/physiology
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Structure-Activity Relationship
MH  - Substrate Specificity
RF  - 124
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - 10.2741/brushia [doi]
PST - epublish
SO  - Front Biosci. 1999 Sep 15;4:D618-41. doi: 10.2741/brushia.