Lecture 14 - 10/19/11 Second Messengers and Effectors TH
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Unformatted text preview: 10/19/11 Second Messengers and Effectors TH
 
 
DOPA DDC
 DBH
 PNMT
 1 10/19/11 Substrate
Specificity
for
Protein
Kinases
 1.  Amino
acid
specificity
 2.  Sequence
specificity
(primary
structure)
 3.

Secondary
and
TerEary
Structure
 2 10/19/11 4.

Spa+al
Loca+on
in
Cell
 3 10/19/11 Protein
Kinase
Ac+va+on
 (PKA)
 PS
 PS
 Adrenaline
 4 10/19/11 Protein
Kinase
C
 1.  Ca
binding
and
requirement
for
acEvity
 2.  Phospholipid
binding
and
requirement
for
acEvity
 3.  DAG
binding
and
acEvaEon
 5 10/19/11 AcEvaEon
mechanism
of
protein
kinase
C
(C‐kinase)
 A
 AcEve
 InacEve
 PS,
phosphaEdyl
serine
 DAG,
diacyl
glycerol
 ,
pseudosubstrate
domain
 C2
 C1
 The graphic depicts C2 domain of protein kinase C (PKC) beta isoform. Spheres represent calcium cations Ca2+. Scene depicts putative orientation of the domain upon interaction with biological membranes (represented by the plane). The protein fold consists of two sets of beta-pleated sheets (yellow and blue arrows) interconnected by flexible loops. 6 10/19/11 DAG
 C2
 C1
 PMA
 The
graphic
depicts
C1
domain
of
protein
kinase
C
(PKC)
delta
isoform.
Spheres
represent
zinc
caEons
which
 are
coordinated
by
side
chain
residues
and
are
playing
a
major
role
in
keeping
overall
structural
stability
of
 the
domain.
Scene
depicts
putaEve
orientaEon
of
the
domain
upon
interacEon
with
biological
membranes
 (represented
by
the
plane).
Depicted
in
red
ball‐and‐sEck
model
is
a
phorbol‐13‐acetate
‐
nonphysiological
 acEvator
of
PKC,
which
increases
affinity
of
the
C1
domain
towards
biological
membranes.
 7 10/19/11 8 10/19/11 Ca++
Signaling
 Ion
channels
 Ca‐dependent
enzymes
 Ca‐dependent
kinases
 Structural
proteins
 Nuclear
proteins
 
 





CALMODULIN
 endoplasmic
 9 10/19/11 some
calmodulin‐binding
proteins
with
their
locaEons
and
funcEons
 10 10/19/11 11 10/19/11 12 10/19/11 13 10/19/11 Ca/CaM
regulaEon
of

 Calcium
Channels
 14 10/19/11 AcEvaEon
of
CaM
Kinase
II
 or
IP
3
 domain
 15 10/19/11 Figure 15-44 Molecular Biology of the Cell (© Garland Science 2008) Figure 15-45 Molecular Biology of the Cell (© Garland Science 2008) 16 ...
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