Biology 416- Singaling- Gene Expression- 3/27/08

Front 1

Mechanism of Ca2+ release after fertilization of animal eggs

Back 1

Activated sperm binds to the egg surface  local Ca2+ release, exocytosis of cortical granule contents.

Wave of Ca2+ release and exocytosis moves across the egg  formation of fertilization envelope, blocking additional sperm entry.

Ca2+ also necessary for activation of egg, allowing embryonic development to begin.

Front 2

Short-term cell signaling responses

Back 2

rapid, usually easily reversible, often modifications of pre-existing proteins

Front 3

Longer-term cell signaling responses

Back 3

slower, usually are changes in transcription of genes - expression of new proteins, loss of other proteins

Front 4

What cell processes are affected by changes in gene expression?

Back 4

Cell division, differentiation, cell-cell communication, immune response

Disruption can lead to cancer, birth defects, autoimmune problems, immunodeficiency, and diabetes.

Front 5

How are changes in gene expression mediated?

Back 5

by binding of transcription factors to control regions near eukaryotic genes: promoters, enhancers, other upstream regulatory sites.

Front 6

What are transcription factors?

Back 6

proteins

Front 7

What are regulatory sites?

Back 7

sequences in the DNA

Front 8

What happens when a transcription factor binds to a regulatory site?

Back 8

turns on transcription of the genes regulated by those sites.

Front 9

TGFB signaling pathway

Back 9

TGF binds to receptor  association and activation of receptor subunits.

Kinase activity of receptor phosphorylates R-Smad  conformational change, exposing NLS.

R-Smads bind with a co-Smad and with -importin.

Complex translocates into the nucleus, partially dissociates with the help of Ran-GTP.

R-Smad/co-Smad complex associates with a nuclear transcription factor  binding to regulatory sequences of target gene.

Front 10

Ras/MAP kinase pathway

Back 10

Activated by binding of ligand to almost all receptor tyrosine kinases (function as dimers) and many cytokine receptors.

Signal transduction pathway contains three sequentially acting protein kinases (Raf, MEK, and MAP kinase)

MAP kinase can enter the nucleus and phosphorylate many different proteins, including transcription factors important in differentiation and the cell cycle.

Front 11

Ras

Back 11

a monomeric G protein - part of the GTPase superfamily of switch proteins

Front 12

Receptor tyrosine kinase (RTK)Pathway

Back 12

Extracellular part of protein binds ligand  Aggregation of the receptor  Phosphorylate each other on tyrosine residues on interior region of receptor.

Front 13

Ras/MAP kinase pathway

Back 13

Binding of ligand to receptor  activation of Ras, binding of GTP.

Activated Ras binds Raf regulatory domain  conformational change. Cleavage of GTP, release of Raf.
Raf phosphorylates MEK, activating it.
MEK phosphorylates MAP kinase, activating it.
Active MAP kinase dimerizes, translocates to nucleus, phosphorylates transcription factors  turns on target genes.

Front 14

G protein-coupled receptors (GPCRs)Structure

Back 14

structure always contains seven membrane-spanning domains.

Front 15

G protein-coupled receptors

Back 15

Receptor binding  activation of adenyll cyclase  increase in cAMP levels  activation of PKA.

Catalytic subunits of PKA  nucleus, phosphorylate CREB, activating it.

CREB binds co-activator, stimulating transcription of target genes

Front 16

CRE

Back 16

cAMP-response element

Front 17

Wnt signaling pathway

Back 17

Controls brain development, limb patterning, and organogenesis. Controls formation of osteoblasts in humans  affect bone density.