MCDB 3145 Molecular & Cell Biology II

Part IV. Cell Reproduction and Cell Signaling

Spring 2016, Stowell

Cell Reproduction

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

Chiasma

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)

Lipid

signaling

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

Cytochrome C

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

Xue Lab