Transcript Fundamentals of Cell Biology

Fundamentals of Cell Biology
Chapter 11: Signal Transduction
and Cellular Communication
Chapter Summary: The Big Picture (1)
• Chapter foci:
– Structure of a signaling pathway
– Types of signals cells detect and the role of the
receptor
– Molecules most commonly found in signaling
pathways
– Examples of well known signaling pathways
examined in order to understand all of the
aforementioned
Chapter Summary: The Big Picture (2)
• Section topics:
– Signaling molecules form communication
networks
– Cell-signaling molecules transmit information
between cells
– Intracellular signaling proteins propagate
signals within a cell
– A brief look at some common signaling
pathways
Signaling molecules form communication
networks
• Key Concepts:
– Signaling networks relay information from the
extracellular environment to the interior of a cell.
– The basic unit of a signaling network is a signal
transduction pathway, which carries one specific
signal in a single direction from the source (a
receptor) to the effector.
– Most signal transduction pathways are comprised of
several different molecules that activate each other
in a carefully controlled sequence of binding
interactions.
Signal Transduction Pathway
•
•
function: convert
extracellular information
into an appropriate
cellular response
composed of:
– signals
– receptors
– signaling proteins
– second messenger
molecules
Figure 11.01:
Simple
schematic of
signal
transduction
pathways.
Signal Transduction Pathway
Figure 11.02: Signaling pathways use linear, convergent, divergent, and branched signaling pathways to
generate complex responses to external signals.
Signaling networks are long and
complex
Cell-signaling molecules transmit
information between cells
• Key Concepts:
– Signals arise from the extracellular space, and
must bind a receptor to be effective.
– Most signals are molecules that cannot penetrate
the plasma membrane, so they bind to receptor
proteins on the cell surface. Those signals can
then pass through membranes and are bound by
receptors in the cytosol.
– Receptors are grouped into six classes, according
to their structure, binding partners, and cellular
location.
Signaling begins when ligand binds to
target receptor
• Types of ligands:
– Membrane impermeable
• neurotransmitters
– Membrane permeable
• estrogen, testosterone
– Physical signals
• pressure, temperature, light
6 classes of receptors detect a vast array of environmental stimuli
Figure 11.03:
Receptors are
grouped into six
classes based on
their structure
and cellular
location.
G-protein coupled receptors activate G proteins
Figure 11.04: The general structure of a seven transmembrane receptor.
Receptor protein kinases phosphorylate signaling proteins
Figure 11.05: Model of
growth factor receptor
activation.
Receptor protein kinases phosphorylate signaling proteins
Figure 11.06:
Serine/threonine kinase
receptor activation leads to
phosphorylation of a
signaling protein.
Figure 01.14C: The 20 most common amino acids are classified into three classes
based on the structure of their side chains.
Phosphoprotein phosphatases remove phosphate groups from
signaling proteins
Figure 11.07: Protein phosphatases break the phosphester bond linking phosphate groups
to serine, threonine, and tyrosine side chains.
Guanylyl cyclases produce the signaling molecule cyclic GMP
Figure 11.08: Receptor guanylyl
cyclases are homodimeric
receptors that contain a
cytoplasmic domain that
converts GTP into cyclic GMP.
Ion channel receptors permit ion fluxes
Figure 11.09:
Ligand-gated
channels typically
form a central
pore that opens
when a ligand
binds to the
receptor.
Transmembrane scaffolds recruit intracellular signaling proteins
Figure 11.10:
Integrin
receptors form
signaling
scaffolds.
Nuclear receptors are transcription factors
Figure 11.11: The steroid
receptor binds to steroid
hormones when they diffuse
into the cytosol.
Intracellular signaling proteins propagate
signals within a cell
• Key Concepts:
– Signaling proteins rapidly transmit and amplify
signal information.
– As information passes through a signal transduction
pathway, it often changes physical form.
– Signaling proteins are grouped into six classes
based on their structure, location, and mechanism of
signal transmission.
– Second messengers are non-protein molecules that
link signaling proteins together in signal transduction
pathways.
G proteins are molecular switches
Figure 11.12: The GTPase cycle repeats continuously, shifting the G protein between active
and inactive states like a switch.
G proteins are molecular switches
Figure 11.13: A
heterotrimeric G
protein signaling cycle.
GTPase cycle
Protein kinases phosphorylate
downstream signaling proteins
Figure 11.14: Protein kinases add phosphate groups to signaling proteins and effectors.
Lipid kinases phosphorylate phopsholipids
Figure 11.15: Lipid kinases add phosphates to phospholipids.
Calcium fluxes control calcium-binding proteins
Figure 11.16: Calmodulin is
an example of a calcium
sensitive signaling protein.
Adenylyl cyclases form cyclic AMP
Figure 11.17: Adenylyl cyclase is a target of competing
regulatory pathways.
Figure 11.18:
Phosphodiesterase
cleaves the
phosphoester bond
between the
phosphate and the 3'
carbon of ribose,
converting cAMP to
AMP.
Adaptors facilitate binding of multiple signaling proteins
Signaling, an overview
Guanylyl
S/TKR Cyclase
Ligand
Scaffold Gated Ion
(Integrin) Channel
RTK
Steroids
GPCR
Signaling
Proteins
HeteroProtein
trimeric G Kinases
Proteins
Lipid
Kinases
Calcium
Binding
Proteins
Adenylyl
Cyclases
Adaptor MonoProteins meric G
Proteins
Second
Messengers
Ions
Lipids +
Hydrocarbons
Steroid
Nucleotides
Receptors
iClicker Time
What causes the α and βγ subunits of heterotrimeric G
proteins to dissociate from each other?
a.
b.
c.
d.
e.
Phosphorylation of the α subunit
Phosphorylation of the G protein-linked receptor
Phosphorylation of GEF
A change in shape in G protein linked receptors
Cleavage of GTP to GDP by the α subunit.
A brief look at some common signaling
pathways
• Key Concepts:
– Hundreds of different receptors, signaling proteins, and
effectors combine into a complex network of interacting
pathways within a single cell.
– Despite the tremendous complexity of signaling
networks, many share common features that help set
the standard for our current understanding of how signal
transduction pathways function.
– Some signal transduction pathways trigger short-term
cellular changes via very long and complex sets of
signaling interaction, while others contain very few steps
and have relatively long-term effects on cells.
Protein tyrosine kinase signaling pathways control
cell growth and migration
Figure 11.19: A simplified version
of an FGF signaling pathway.
Heterotrimeric G protein signaling pathways regulate a
great variety of cellular behaviors
Figure 11.20: A sample cAMP signaling
pathway.
Phospholipid kinase pathways work in cooperation
with protein kinase and G protein pathways
Figure 11.21: The phosphoinositol 4,5-bis phosphate (PIP2) signaling pathway.
Phospholipid kinase pathways work in cooperation
with protein kinase and G protein pathways
Figure 11.22: PIP2
phosphodiesterase and IP3
phosphatase inhibit PIP2
signaling.