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Death
Fig.12-2
Signaling Molecules
steroid hormones NO and CO neurotransmitters peptide hormones, neuropeptides, and growth factors eicosanoids
Cholesterol
estrogen progesterone
Ecdysone
(insect hormone)
Structure of Steroid Hormones, Thyroid Hormone, Vitamin D3, and Retinoic Acid
Estrogen Action
histone acetyltransferase
histone deacetylase
Fig. 6-32
Histone acetylation
kidney
Peptides as Hormones
Peptide hormones insulin, glucagon, FSH, and prolactin Neuropeptides oxytocin, vasopressin, enkephalins, and endorphins. Polypeptide growth factors NGF (nerve growth factor)1950 EGF (epidermal growth factor) PDGF (platelet-derived growth factor) cytokines
Fig.23-5
insulin
cycloxygenase
lipoxygenases
thromboxane synthase
The eicosanoids are rapidly broken down and therefore act locally in autocrine or paracrine signaling pathway.
arachidonic acid
cyclooxygenase
aspirin
lipooxygenase
prostaglandin H2
thromboxane synthase
leukotriene B4
prostaglandin A2
reduces inflammation and pain
thromboxane A2
aspirin also reduces platelet aggregation and blood clotting
G Protein-Coupled Receptor
The largest family of cell surface receptors
More than a thousand such G protein coupled receptors are identified
heterotrimeric G proteins
epinephrine = adrenaline
b-adrenergic receptor
Regulation of G Proteins
Activity of the subunit is terminated by hydrolysis of the bound GTP, and the inactive GDP-bound subunit then reassociates with the b complex.
In the inactive state, the subunit is bound to GDP in a complex with b and .
Hormone binding induces an interaction of the receptor with the G protein, stimulating the release of GDP and the exchange of GTP.
Gi
Gi
the Gib subunits act directly to open K+ channels in the plasma membrane, which has the effect of slowing heart muscle contraction.
The effect of acetylcholine on heart muscle cells is to a. stimulate one contraction. b. increase the rate of beating. c. decrease the rate of beating. d. relax the heart.
Neurotransmitters act by binding to receptors that are a. ligand-gated ion channels. b. G protein linked receptors. c. tyrosine-kinase receptors. d. Both a and b
autophosphorylation by cross-phosphorylation
1) 2)
The effects of SH2-phosphotyrosine binding 1) 2) 3) Lead to their association with other proteins Pormote phosphorylation Stimulate enzymatic activities
Figure 13.16 Complex between an SH2 Domain and a Phosphotyrosine Peptide Kinases
Cytokine Receptors
JAK Src
Receptors for IL-3, IL-5, and GM-CSF share a common chain CD131 or bc
TNF-receptor family
TNF receptors I and II CD40, Fas (Apo1), CD30, CD27 Nerve growth factor receptor
CCR1-5, CXCR1-4
Src family, which consists of Src and eight closely related proteins
Annu.Rev.Cell Dev.Biol.13:513.1997
some Src
Splicing of the CD45 gene transcript in nave T cells includes the A, B,and C exons
CD45RA
Both receptor components have a serine/threonine protein kinase domain in the cytoplasmic region
cAMP and cGMP Phospholipid and Ca2+ Ras, Raf, and MAP kinase The JAK/STAT
The chain of reactions leading from epinephrine receptor to glycogen phosphorylase provides a good illustration of signal amplification during intracellular signal transduction.
How would overexpression of protein phosphatase 1 affect the induction of cAMP-inducible genes in response to hormone stimulation of appropriate target cells? Would protein phosphatase 1 affect the function of cAMP-gated ion channels involved in odorant reception?
[cGMP] cGMP gated ion channel close Na+K+ ATPase hyperpolize plasma membrane
500 nM
Hydrolysis of PIP2
One of the most widespread pathways of intracellular signaling is based on the second messengers derived form PIP2
phosphatidylinositol 4,5-bisphosphate
Fig.12-19 Lehninger
PIP2
0.1 mM
Fig. 13-28
Function of Calmodulin
Many of the effects of Ca2+ are mediated by the Ca2+ binding protein calmodulin
0.1mM 0.5mM
Fig. 15-41.
membrane depolyrization Plasma membrane voltage-gated Ca2+ channel open Intracellular Ca2+ ryanodine receptors open, more Ca2+ Release of neurotransmitters
Activity of PI 3-Kinase
phosphatidylinositol 3,4,5-triphosphate
Figure 13.33
GTPase-activating proteins
Figure 13.34
Figure 13.35
Figure 13.36
Figure 13.37
Figure 13.38
Figure 13.39
Integrin Signaling
focal adhesion kinase
Figure 13.40
Figure 13.40
Figure 13.41
Figure 13.42
Figure 13.43
Induction of R7 Differentiation
Figure 13.44
(EGF)
Figure 13.44
Figure 13.45
Hedgehog Signaling
Figure 13.46
Figure 13.47
Notch Signaling
Characterization of apoptosis Ced-9, Ced-4, Ced-3, caspases Bcl-2 Death signal and its receptors - Fas Survival signal -
DNA fragmentation
Ced-4 and its mammalian homolog (Apa-1) bind to caspases and promote their activation
Other members of the Bcl-2 family,induce caspase activation and promote cell death