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Lecture 10

Lecture 10

Course Code
Darrel Desveaux

of 4
Lecture 10
Cell Communication: General Concepts and Principles
Cell Communication Through Signaling
oUnicellular organisms
Sense signals in growth environment
Eg. High [nutrients]
oMulticellular organisms
Complex signaling networks
Cells within organism carefully regulated
Why is Signaling Important? Example: Regulation of Cell Proliferation
oIf cell doesnt respond appropriately cancer
oChart of major signaling pathways relevant to cancer in human
cells (Figure 20-37)
oCancer misregulation of growth cells
oOveractive signals regulate proliferation
Why is Signaling Important? Example: Regulation of Cell Movement
oSlime Mold (unicellular)
Attracted to cAMP chemotaxis moves toward high
concentration of chemical
Signal for single cells to aggregate to form slug
oMicropipette with cAMP
Movement by extending a new pseudopod
Signal Molecules and Receptors
o1) Cell surface receptors
Bind to hydrophilic ligand
o2) Intracellular receptors
Bind to hydrophobic signaling molecules
Transported by carrier proteins in extracellular fluid and
deliver to cells
Because not soluble
Classes of Cell Surface Receptors in Animals
o1) Ion-Channel-linked receptors
(ligand gated ion channels)
Eg. Regulated by neurotransmitters
o2) G-protein-linked receptors (GPCR)
Largest family in animals
>800 genes in human genome
Receptors to visual, taste, smell, and many other
o3) Enzyme-linked receptors
Cytosolic domain has enzymatic activity or is associated
with an enzyme
Receptor tyrosine kinases (RTKs)
TGFb receptor serine/threonine kinases
Cytokine receptors (Jak/STAT pathway)
o4) Other receptors
Eg. Hedgehog, Wnt, Notch receptors
Important roles in animal development
Specifying cell types
Signaling pathways gene regulation
*Transmembrane domains; include protein degradation
to activate pathway
Cell Surface Receptors in Plants
oEnzyme-linked receptors:
Receptor serine/threonine kinases
Largest family in plants
Roles in development, growth, disease, resistance
to pathogens
Histidine kinases
Receptors for plant hormones
Intracellular Signaling Pathways (Figure 15-1)
oActivation of intracellular signaling proteins
oCascade: one protein activates another goes to effector
proteins (metabolic enzyme, gene regulatory protein,
cytoskeletal protein) and alters the systems of the body
Intracellular Signaling Pathways
oIntracellular signaling proteins
Large intracellular signaling molecules
oFunction to activate next signaling protein in pathway
(A) Protein kinases phosphorylation of proteins
(B) GTPases (also called GTP-binding proteins)
*Are found in cascades
oFunction to generate second messengers (amplification step)
Adenylyl cyclase produces cAMP, which then activates
other proteins and amplifies signal
Intracellular Signaling Pathways
oSecond messengers
Small intracellular signaling molecules
Large increase in [2nd messenger]
Changes activity of enzymes and other proteins
Ca2+, cAMP, cGMP (water soluble)
1,2-diacylglycerol (DAG) etc. (cell membranes)
Cell Communication: G-Protein-linked Cell-surface Receptors
G-Protein-linked Receptors in Animals
oMost abundant
oReceptor: 7 TM domains
N-terminus and some TM
Ligand binding
oTrimeric G-protein
Alpha, beta, gamma subunits
G-alpha initially bound to GDP
oSignal binding to receptor
Conformational changes in alpha-subunit GTP bound
oAlpha-subunit and Beta-gamma complex
Can activate target proteins
G-Protein-linked Receptors
oExamples of alpha-subunit targets:
o1) Phospholipase C-beta
Cleaves an inositol phospholipid in lipid bilayer
Form 2nd messengers
DAG and IP3
Increase in cytosolic Ca2+
Activation of protein kinase C (PKC)
o2) Adenylyl cyclase
G-Protein linked Receptors: Signal Amplification
Single-receptor ligand
Activate many G-alpha subunits
Lateral diffusion of lipid anchored G-alpha
Each activated G-alpha subunit