Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

PRINCIPLES OF CELL SIGNALING
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(A) PREFORMED SIGNALING COMPLEX
ON A SCAFFOLD PROTEIN
CYTOSOL
inactive receptor
scaffold
protein
3
inactive
intracellular
signaling proteins
signal molecule
1 1
2
3
2
downstream
signals
activated receptor
plasma membrane
activated
intracellular
signaling proteins
Figure 15–10 Three types of intracellular
signaling complexes. (A) A receptor and
some of the intracellular signaling proteins
it activates in sequence are preassembled
into a signaling complex on the inactive
receptor by a large scaffold protein.
(B) A signaling complex assembles
transiently on a receptor only after the
binding of an extracellular signal molecule
has activated the receptor; here, the
activated receptor phosphorylates itself at
multiple sites, which then act as docking
sites for intracellular signaling proteins.
(C) Activation of a receptor leads to the
increased phosphorylation of specific
phospholipids (phosphoinositides) in
the adjacent plasma membrane; these
then serve as docking sites for specific
intracellular signaling proteins, which can
now interact with each other.
(B) ASSEMBLY OF SIGNALING COMPLEX ON AN ACTIVATED RECEPTOR
inactive receptor
signal molecule
1
inactive
intracellular
signaling
proteins
2
3
activated
intracellular
signaling
proteins
downstream
signals
2
3
1
P
P
P
activated receptor
(C) ASSEMBLY OF SIGNALING COMPLEX ON PHOSPHOINOSITIDE DOCKING SITES
inactive
receptor
specific phospholipid
molecules
(phosphoinositides)
signal molecule
activated receptor
hyperphosphorylated
phosphoinositides
P
P
P
P
P P P
P P P
1
2
1
inactive intracellular
signaling proteins
2
activated intracellular
signaling proteins
downstream
signals
enable the protein they are part of to dock on the membrane and interact with
other similarly recruited signaling proteins (see Figure 15–10C). Some signaling
proteins consist solely of two or more interaction domains and function only as
adaptors to link two other proteins together in a signaling pathway.
Interaction domains enable signaling proteins to bind to one another in multiple
specific combinations. Like Lego® bricks, the proteins can form linear or
MBoC6 m15.21/15.10
branching chains or three-dimensional networks, which determine the route
followed by the signaling pathway. As an example, Figure 15–11 illustrates how
some interaction domains mediate the formation of a large signaling complex
around the receptor for the hormone insulin.