PLCbeta -> DAG <-> PKC

(DAG is a receptor that activates PKC)

Signal

Receptor

Signal transduction

Autocrine

Contact dependent

Paracrine

Endocrine

Synaptic

Secreting cell produces signal and responds to the signal

"cell talks to itself"

Signaling cell and responding cell are fairly close together

Signal may be unstable, degraded, or doesn't diffuse very far

- Amino acids and derivatives

- Nerotransmitter (ACh)

- Hormones

- Eicosanoids

- Protein/ polypeptides

- G-protein coupled receptors

- Receptor Protein Tyrosine Kinase

- Ligand Gated Channels

- Steroid Hormone Receptor

- Amino (NH2) group in ECF, Carboxyl (COOH) group in cytosol

- Ligand binds ECF side, G-Protein binds on Cytosolic side

- Crosses membrane 7 times

Heterotrimeric (3 subunits)

Alpha, Beta, and Gamma

Alpha and Gamma link to membrane lipids

In the cytoplasmic domain:

- Receptor becomes phosphorylated (g-protein coupled receptor kinase)

Arrestins bind to phosphorylated receptor

- prevents G-protein binding

- Arrestins can also bind to clathrin (endocytose the receptors) bring to lysosome for degredation, or dephosphorylate the receptors and send back to the PM (recycle)

cAMP

Ca++

Phospholipid derivatives - IP3, DAG, PIP3 (cytoplasmic leaflet can modify)

IP3 and DAG, these are (sometimes) produced by phospholipase cBeta (PLcB)

-Peripheral membrane protein

-Activated by activated G protein "effectors"

Phosphotidyl Inositol (PI) ->

-> kinase (kinases phosphorylate)

-> PIP2 (Original phospholipid with 2 phos added)

FROM HERE GOES TO EITHER

-> IP3

-----OR-----

-> DAG

2nd messenger free in cytosol

- Activates Ca++ in the smooth ER

2nd messenger found in membrane

Diacyl Glycerol (lipids + glycerol)

_________________________

- Docking site for additional signaling molecules

^ KNOW DIS ^

Ligand forms a bridge connecting two receptor proteins

(binds monomers together)

GDP-Ras = ???

GTP-Ras = ???

GDP-Ras = Off

GTP-Ras = On

GEF and GAP recs both

Highly conserved, found in all eukaryotes, and expressed throughout development

Outcome is different in different tissues, same receptor can respond to differently to different signals

A) Differences in signal intensity - also signal duration

B) Differences in downstream pathway

Examples:

RTK -> PLCgamma -> IP3 + DAG

RTK -> PI-3K -> PIP3

RTK -> Ras -> MAPkinase

GPCRs

RTKs

GTP hydrolysis

Endocytosis

- Increase secretion of glucogen from cels of pancrease

- Glucogen binds to receptor livercells and G-protein coupled receptors

A) beta pancratic cells secrete insulin (stored on secretory granules)

B) Insulin receptors (muscle and liver) do their things

Glucose transmitter (glut4) is in membrane of vesicle in the cytosol

Stay in cytosol because of protein AS160

Phosphokinase B phosphorylates AS160 and that inactivates it, allowing vesicle to fuse with PM and glucose xporters remove glucose from blood to cell

Inhibitory protein that prevents vesicle (containing glucose xmitter glut4) to move to the PM

Phospholinase B phosphorylates it, thus inactivating it

Moves transporters to plasma membrane

Stimulate glycogen synthesis

GPCR -> cAMP -> PkA -> cAMP response element CRE

RTK -> RAS -> MAP kinases -> Transcription factors

RTK -> PI-3K -> PIP3 -> PKB -> Phosphorylate and inactivates transcription for apoptosis

Program cell death

Can be stopped when PKB phosphorylates and inactivates transcription for it

Protein kinases -> activate transcription factors

Protein phosphates

Enzymes -> myosin light chain kinase

Enzymes again -> cAMP phosphodiesterase (degrades cAMP) - turns of signal cascade

- Structure and support of cell

- Intracellular transport

- Contractility/motility

- Spatial organization

- Microtubules

- Microfilaments

- Intermediate filaments

- Funct: all cytoskele

- Diameter: largest 25nm

- Subunit: alpha + beta tubulin dimer

- Polarity: polar

- growth site: at + end (beta)

- Funct: Motility, contractility, cell shape

- Dimensions: smallest 8nm

- Subunits: Actin

- Polarity: Yes polar

- Growth Site: At + End (barbed)

- Funct: Structural support

- Dimensions: middle ~10nm

- Subunits: various proteins

- Polarity: no not polar

- Growth site: internal

Intracellular tracks

Spindle fibers

Make up flagella, cilia

Microtubule sub units

alpha = ?

beta = ?

Alpha = - end

Beta = + end

Microtubule asociate proteins

MAPs

- (might) increase stability

- promote assembly/disassembly of microtubles

Move in a stepwise fashion towards one direction (alpha or beta)

Kinesin - move toward + (beta)

Dynein - move toward - (alpha)

Motor protein that moves toward beta direction

Tetramer

2 heavy chains

2 light chains

ATP binding + binding to microtubule at "feet"

Cargo at head

2 heavy chains + a variety of intermediate and light chains

Multimeric

Cargo at head

 Contrains centrioles, 9 triplets of MTs

MTs are anchored in this area by (- , alpha) ends addition of alph bet dimers is to plus end

GTP on alpha ______ be hydrolized to GDP

 GTP on beta ______ be hydrolized to GDP

GTP on alpha cannot

GTP on beta can

Astral

Kinetochore

Polar (overlapping)

Act on overlapping MT

- Push poles apart

(act on astral MT)

-Pulls poles apart

No ribosomes

Site for budding off vesicles

Synthesis of phospholipids and synthesis of cholesterol

Rough ER

Bound ribosomes (cytosolic side)

Integration of transmembrane proteins

Receives proteins to be secreted

ER-Lumen specific proteins

 differ only in terms of the mRNA (messenger RNA) they are translating

SRP

signal recog particle

Binds to signal sequence and ER membrane docking protein

Used to get protein into ER lumen

And causes it to be a bound ribosome

ribosome binds mRNA

Xlation starts

bind SRP

dock on SRP receptor on ER

enter signal

disassociate from SRP receptor

cleave signal

transfers small chains of sugars and move proteins from

Dolichol to asparagine