Chapter 16 Cell Communication

1. General Principles of Cell Signaling 1) Signal can act over long or short range (1) Ways to contact

(2) Contrast between endocrine and synaptic signaling

(2) Gap junctions allow signaling information to be shared by neighboring cells

(1) Animal cell depends on multiple extracellular signals 2) Each cell responds to a limited set of signals (1) Animal cell depends on multiple extracellular signals

(2) Same signal can induce difference response in different target cells

3) Receptors relay signals via intracellular signaling pathways (1) Extracellular signals alter the activity of a variety of cell proteins to change the behavior of the cells

(2) Cellular signaling cascades

4) Nitric oxide crosses the PM and activates intracellular enzyme directly (1) Extracellular signal molecules bind either to cell-surface Rs or intracellular enzyme or Rs

(2) Examples of NO actions NO triggers smooth muscle relaxation in a blood-vessel wall NO activates guanylyl cyclase

5) Nuclear Receptors are ligand-activated gene regulatory proteins (1) Some small hydrophobic hormones bind to intracellular Rs that act as gene regulatory proteins

(2) Nuclear Receptors superfamily Receptors all have a related st.

The binding of ligand to the receptor cause the activation of receptors

Response induced by the activation of a nuclear hormones receptor

6) Cell-surface Rs fall into 3 main classes

7) Intracellular Signaling molecules (1) Most activated cell-surface receptors relay signals via small molecules and a network of intracellular signaling proteins

(2) Many intracellular signals proteins act as molecular switches

(3) Intracellular signaling complex enhance the speed, efficiency, and specificity of the response

(4) Interaction between intracellular signaling proteins are medicated by modular binding domains

8) Cells can adjust their sensitivity to a signal

2. G-protein-linked receptors Inactive G protein

(1) G protein dissociate into two signaling proteins when activated 1) Stimulation of G-protein -linked Rs activates G-protein subunits (1) G protein dissociate into two signaling proteins when activated

(2) G-protein α subunit switches itself off by hydrolyzing its bound GTP

2) Some G proteins regulate ion channels

3) Some G proteins activate membrane-bound enzyme (1) G protein activate adenylyl cyclase Adenylyl cyclase

(2) cAMP concentration rises rapidly in response to an extracellular signal

(3) Extracellular signaling can act slowly or rapidly

Example of slow response

4) IP (inositol phospholipid ) pathway triggers a rise in intracellular Ca2+ Hydrolysis of PI by PI kinase and phospholipase C

IP3 pathway

5) Ca2+ Signal triggers many biological processes (1) Fertilization of an egg by a sperm triggers an increase in cytosolic Ca2+ in the egg

(2) [Ca2+ ] in the cytosol is extremely low Main ways eucaryotic cells maintain a very low concentration of free Ca2+ in their cytosol

(3) Effect of Ca2+ in the cytosol are largely indirect Ca2+/calmodulin

Activation of CaM-kinase II

Rod photoreceptor cell from retina 6) Intracellular signaling cascades can achieve astonishing speed, sensitivity, and adaptability: A look at photoreceptors in the eye Rod photoreceptor cell from retina

Light-induced signaling cascade in rod photoreceptor cell greatly amplifies the light signal

3. Enzyme-linked Rs 1) Receptor tyrosine kinases (1) Phosphorylate themselves 7 superfamily of receptor tyrosine kinases

(2) Activated R tyrosine kinases assemble a complex of intracellular signaling protein

(3) Inhibition of signaling through normal receptor tyrosine kinases by an excess of mutant receptors

(4) Phosphorylated tyrosines serve as docking sites for proteins with SH2 domains

(5) R tyrosine kinases activate the GTP-binding protein Ras

Ras activates a MAP-kinases phosphorylation cascade

organization of MAP-kinases pathway by scaffold proteins in budding yeast

Jak-STAT signaling pathway activated by α-interferon 2) Cytokine receptors activate the Jak-STAT signaling pathway, providing a fast tract to the nucleus Jak-STAT signaling pathway activated by α-interferon

3) TGF-β superfamily signals along receptor serin/threonine kinase and smads

4) Protein kinase network integrates information to control complex cell behavior

Example of signal integration

3. Signaling pathway dependent on regulated proteolysis 1) Receptor protein notch is activated by cleavage (1) Lateral inhibition mediated by Notch and Delta during nerve cell development in Drosophila

(2) Processing and activation of Notch by proteolytic cleavage

2) Wnt binds to Frizzles and inhibit the degradation of β-catenin

3) Hedgehog act through complex of Patched and smoothened

4) Multiple stressful and proinflammatory stimuli act through an NF-kB dependent signaling pathway