MCDB 3145 Molecular & Cell Biology II
Part IV. Cell Reproduction and Cell Signaling
Spring 2016, Stowell
Control of the Cell Cycle
Fusing cells at different cell cycle stages
M and G1 M and S M and G2
Fission yeast (simple)
G1->S
(ATM/Chk2)
Checkpoints
G2->M
(ATR/Chk1)
Importance of cell cycle arrest
Spindle assembly checkpoint
Mad2
L Chang et al. Nature 000, 1-5 (2015) doi:10.1038/nature14471
What happens when the cell exits from Mitosis
-spindle pole disassembly
-Chromosomes decondense
-Nuclear envelope reforms
-Cytokinesis
Formation of the contractile ring
1) Autocrine 2) Paracrine 3) Endocrine
Cell Signalling
Signaling pathways
•Growth factor signaling (EGFR)
•Insulin signaling (insulin receptor)
•G-protein coupled receptors (GPCRs)
•Apoptosis
RECEPTOR TYROSINE KINASES (RTKs)
Example 1: EGFR
growth factor induced
paracrine
Example 2: Insulin Receptor
hormone induced
endocrine
Receptor protein-tyrosine kinase (RTK) signaling
Growth
Factors
?
Cell
proliferation
cAMP
Ca2+
IP3
DAG
cGMP
NO
The epidermal growth factor (EGF) receptor is
a receptor protein-tyrosine kinase (RTK)
Phosphorylated tyrosines serve as
docking sites for SH2-domain
proteins such as Grb2.
In turn, Grb2 interacts with guanine
nucleotide exchange factors
(GEFs), such as SOS, through its
SH3 domains.
GEFs then activate Ras.
EGF signaling
Mitogen activated
protein kinase
GEF GAP
RECEPTOR TYROSINE KINASES (RTKs)
Example 1: EGFR
growth factor induced
paracrine
Example 2: Insulin Receptor
hormone induced
endocrine
Insulin (produced by pancreas)->blood-> InsR on
Liver/muscle/adipose cells
Insulin Receptor (A and B isoforms)
cAMP
Ca2+
IP3
DAG
cGMP
NO
Rhodopsin (photon activated)
GPCRs (Rhodopsin, ligand induced, auto/para/endocrine)
Adenylate cyclase
cAMP response element
How does cAMP/PKA target all these processes?
A-kinase anchor proteins
(AKAPs)
IP3 and DAG
1.2 megadalton
Signaling convergence, divergence and cross-talk
CONVERGENCE
DIVERGENCE
CROSS TALK
RTKs GPCRs
CROSS TALK
APOPTOSIS
Programed Cell Death
Differentiation of Digits
Programmed Cell Death
Figure 12.1
MacBlue Mouse (macrophage expressing fluorescent protein)
Localization of Macrophages
Activation of MOMP (internal cell damage)
Cytochrome C localization
Extrinsic Apoptosis
Initiator Caspases start the pathway
Activation of Cononical Caspases
-Initiator Caspases
Caspase 9(intrinsic) or 8 (extrinsic)
-Executioner Caspases
(Caspase 3)
Pro-Caspase-----Caspase
Recognition of Apoptotic Cell