Fundamentals of Cell Biology

Chapter 11: Signal Transduction and Cellular Communication

• 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 (1)

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 fluxesFigure 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.

• 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.

Intracellular signaling proteins propagate signals within a cell

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

GPCR

Ligand Gated Ion Channel

Protein Kinases

Scaffold (Integrin)

Mono-meric G Proteins

Hetero-trimeric G Proteins

Steroids

Steroid

Receptors

RTKS/TKR

Guanylyl Cyclase

Lipid Kinases

Calcium Binding Proteins

Adenylyl Cyclases

Signaling Proteins

AdaptorProteins

Second Messengers

IonsLipids +

HydrocarbonsNucleotides

iClicker Time

What causes the α and βγ subunits of heterotrimeric G proteins to dissociate from each other?

a. Phosphorylation of the α subunitb. Phosphorylation of the G protein-linked receptorc. Phosphorylation of GEFd. A change in shape in G protein linked receptorse. Cleavage of GTP to GDP by the α subunit.

• 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.

A brief look at some common signaling pathways

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.