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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

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fundamentals of cell biology

Fundamentals of Cell Biology

Chapter 11: Signal Transduction and Cellular Communication

slide2

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
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
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
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 pathway6
Signal Transduction Pathway

Figure 11.02: Signaling pathways use linear, convergent, divergent, and branched signaling pathways to generate complex responses to external signals.

cell signaling molecules transmit information between cells
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
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
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
G-protein coupled receptors activate G proteins

Figure 11.04: The general structure of a seven transmembrane receptor.

receptor protein kinases phosphorylate signaling proteins
Receptor protein kinasesphosphorylate signaling proteins

Figure 11.05: Model of growth factor receptor activation.

receptor protein kinases phosphorylate signaling proteins13
Receptor protein kinasesphosphorylate signaling proteins

Figure 11.06: Serine/threonine kinase receptor activation leads to phosphorylation of a signaling protein.

slide14
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
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
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
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
Transmembrane scaffolds recruit intracellular signaling proteins

Figure 11.10: Integrin receptors form signaling scaffolds.

nuclear receptors are transcription factors
Nuclear receptors are transcription factors

Figure 11.11: The steroid receptor binds to steroid hormones when they diffuse into the cytosol.

slide20

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
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 switches22
G proteins are molecular switches

Figure 11.13: A heterotrimeric G protein signaling cycle.

protein kinases phosphorylate downstream signaling proteins
Protein kinases phosphorylate downstream signaling proteins

Figure 11.14: Protein kinases add phosphate groups to signaling proteins and effectors.

lipid kinases phosphorylate phopsholipids
Lipid kinases phosphorylate phopsholipids

Figure 11.15: Lipid kinases add phosphates to phospholipids.

calcium fluxes control calcium binding proteins
Calcium fluxes control calcium-binding proteins

Figure 11.16: Calmodulin is an example of a calcium sensitive signaling protein.

adenylyl cyclases form cyclic amp
Adenylyl cyclases form cyclic AMP

Figure 11.18: Phosphodiesterase cleaves the phosphoester bond between the phosphate and the 3' carbon of ribose, converting cAMP to AMP.

Figure 11.17: Adenylyl cyclase is a target of competing regulatory pathways.

signaling an overview
Signaling, an overview

Ligand Gated Ion Channel

Scaffold (Integrin)

Guanylyl Cyclase

S/TKR

Steroids

RTK

GPCR

Signaling Proteins

Hetero-trimeric G Proteins

Mono-meric G Proteins

Protein Kinases

Calcium Binding Proteins

Lipid Kinases

Adenylyl Cyclases

AdaptorProteins

Second Messengers

Steroid

Receptors

Lipids +Hydrocarbons

Nucleotides

Ions

iclicker time
iClicker Time

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

a. Phosphorylation of the α subunit

b. Phosphorylation of the G protein-linked receptor

c. Phosphorylation of GEF

d. A change in shape in G protein linked receptors

e. Cleavage of GTP to GDP by the α subunit.

slide31

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
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
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 pat hways
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 pat hways35
Phospholipid kinase pathways work in cooperation with protein kinase and G protein pathways

Figure 11.22: PIP2 phosphodiesterase and IP3 phosphatase inhibit PIP2 signaling.