Transcript Unit Five - South Eastern School District

UNIT FIVE
CHAPTER 9
CELL COMMUNICATION
CHAPTER 9
OVERVIEW
• Communication between cells is critical to survival
• Cell signaling requires a signaling molecule, or ligand, and a receptor protein
to function
• Interaction between the ligand and receptor is called signal transduction
• The result of transduction is cellular response
TYPES OF SIGNALS
• Peptides
• Large proteins
• Amino acids
• Nucleotides
• Steroids
• Lipids
• Nitric oxide
HOW DOES THIS WORK?
• Shape of the ligand and the
receptor need to be complementary
• Binding induces a shape or
conformational change
• Conformation change produces a
cellular response
FOUR TYPES OF SIGNALING
Determined by distance from source to receptor
Fifth type—autocrine—cells send signals to themselves
WHY HAVE SIGNALING?
• To produce a response
• The key to producing the response is phosphorylation
• Phosphorylation of proteins alters their function and essentially turns them “on”
or “off”
PROTEIN KINASES
AND PHOPHATASES
Protein kinases add a phosphate
The phosphate attaches to the –OH group of
either serine, threonine, or tyrosine
Two classes: serine-threonine kinases and
tyrosine kinases
Phosphatases reverse the action of protein
kinases
RECEPTORS ARE DEFINED BY LOCATION
• Intracellular receptors bind
hydrophobic ligands
• Cell surface or membrane receptors
bind hydrophilic receptors
MEMBRANE RECEPTORS
SECOND MESSENGERS
• Membrane proteins sometimes utilize other cytoplasmic substances to relay
messages
• The substances can be ions or other small molecules, but they are referred to
as second messengers
• Cyclic adenosine monophosphate (cAMP)
• Calcium ions (Ca+2)
INTRACELLULAR RECEPTORS
• Small lipid soluble molecules can pass through the membrane
• Steroids are one of the simplest and most direct intracellular receptors
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Cortisol
Estrogen
Progesterone
Testosterone
STEROID RECEPTOR ACTION
• Primary function of steroid receptors is to regulate gene expression
• Each receptor has three functional domains
• Hormone-binding domain
• DNA-binding domain
• Domain to interact with coactivators to regulate level of gene transcription
ROLE OF COACTIVATORS
• Large number of coactivators
• Receptors can interact with many coactivators eliciting different responses
• Estrogen has different effects in uterine vs. mammary tissue, the difference is
due to coactivators
OTHER INTRACELLULAR RECEPTORS
• Guanylyl cyclase binds NO allowing it to catalyze the synthesis of cyclic
guanosine monophosphate (cGMP), which can cause muscle relaxation
• Acetylcholine binds epithelial cells causing a release of Ca+2 that stimulates
NO production that causes cGMP production to relax epithelial smooth muscle
• Sildenafil or Viagra function using the cGMP pathway
SIGNAL TRANSDUCTION THROUGH RTKS
• Receptor tyrosine kinases (RTKs)
• Influence: cell cycle, metabolism, cell migration, cell proliferation, virtually all
aspects
• Alterations to RTK function can result in cancer
• Receptors can get stuck in the “on” position
• Plants have similar receptors, Serine-Threonine Kinases
RTKS FUNCTION THROUGH PHOSPHORYLATION
THE INSULIN RECEPTOR
Docking proteins are exemplified by the insulin receptor
Insulin response protein binds to the phosphorylated receptor
Signal passed from the response protein to glycogen synthase
Glucose gets converted to glycogen thereby lowering blood sugar
ADAPTER PROTEINS
A class of proteins that bind phosphotyrosines
Do not participate in signal transduction, but act as a link between
receptors and downstream events
RAS
CASCADES CAN AMPLIFY SIGNALS
• Mitogen activated protein kinases (MAP kinases)
• Mitogen is a chemical that stimulates cell division
• MAP kinases are activated by a phosphorylation cascade or kinase cascade
• Amplification comes from the ability of the enzymes to run the reactions over
and over—small number of molecules give a large response
SCAFFOLD PROTEINS
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Used to organize cascades in the
cytoplasm to increase effectiveness
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Physically arranged sequence is more
efficient than a sequence that relies on
diffusion to move molecules
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Disadvantage—reduces amplification
CLOSER LOOK AT RAS
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It is the link between RTK and MAP
kinases
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RAS is mutated in many human tumors
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Can be terminated by GTPase activity,
which is controlled by GAP proteins
It is a small GTP binding protein
Active when bound to GTP and inactive
when bound to GDP
Works by exchanging GDP for GTP
through GEFs (guanine exchange
factors)
RTK INACTIVATION
• Two methods of turning “off” RTKs
• Dephosphorylation
• Internalization—receptor is taken up by vesicle and degraded and recycled
G PROTEIN COUPLED RECEPTORS (GPCR)
• Single largest category of receptors in animal cells
• Diverse ligands: ions, organic odorants, peptides, proteins, lipids, photons
• Seven transmembrane domains
• Found in virtually all eukaryotic cells
• Latest count, 799, about half involved in taste and smell
• In mice, 1000, with five subgroups
LINKING RECEPTORS
AND EFFECTORS
GPCRs are the link between the receptor
and the effector proteins that elicit responses
Acts as a switch, when “on” the effectors can
cause a cellular response
EFFECTORS CAN PRODUCE MULTIPLE RESPONSES
• Many effectors activated by G proteins have multiple responses due to
second messengers
• Common second messengers:
• Adenylyl cyclase-produces cAMP and IP3
• Phospholipase C—produces DAG
CYCLIC AMP
cAMP activates protein kinase A (PKA), which
adds phosphates to other proteins
Effect depends on cell type
In muscle cells PKA cause glucose to
manufactured and glycogen production to be
inhibited
Vibrio cholera produces a toxin to turn “on”
GCPR, causing large cAMP production,
increased Cl- ions to leave the intestine and
bring water with them, result: diarrhea
INOSITOL PHOSPHATES AND CALCIUM
INOSITOL PHOSPHATES
• Most common is PIP2
• Substrate of effector protein
phospholipase C, which cleaves PIP2
to make DAG and IP3
CALCIUM
• Ca+2 ions are normally low in
cytoplasm, but high in the ER
• IP3 can be bound by ER receptor to
release Ca+2
CALMODULIN
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Ca+2 can bind a 148 amino acid
protein called calmodulin
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When 4 Ca+2 ions bind then calmodulin
can activate other proteins
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Protein kinases
Ion channels
Cyclic nucleotide phosphodiesterases