 Regulation - cells need to control cellular processes.  Environmental Stimuli - cells need to be able to respond to signals from their environment.

 A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Receptor  factor a factor a   a Exchange of mating factors Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell a/  1 2 3

 Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 In many cases, animal cells communicate using local regulators, messenger molecules that travel only short distances  In long-distance signaling, plants and animals use chemicals called hormones Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

1. Reception - receiving the signal. 2. Transduction - passing on the signal. 3. Response - cellular changes because of the signal.

 The target cell’s detection of a signal coming from outside the cell.  May occur by:  Direct Contact  Through signal molecules

 When molecules can flow directly from cell to cell without crossing membranes.  Plants - plasmodesmata  Animals - gap junctions

 May also occur by cell surface molecules that project from the surface and “touch” another cell.

 The actual chemical signal that travels from cell to cell.  Often water soluble.  Usually too large to travel through membranes.  Double reason why they can’t cross cell membranes.

 Behave as “ligands”: a smaller molecule that binds to a larger one.

 Usually made of protein.  Change shape when bind to a signal molecule.  Transmits information from the exterior to the interior of a cell.

1. G-Protein linked 2. Tyrosine-Kinase 3. Ion channels 4. Intracellular

 Plasma membrane receptor.  Works with “G-protein”, an intracellular protein with GDP or GTP.

 GDP and GTP acts as a switch.  If GDP - inactive  If GTP - active

 When active (GTP), the protein binds to another protein (enzyme) and alters its activation.  Active state is only temporary.

Fig. 11-7b G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme

 Very widespread and diverse in functions.  Ex - vision, smell, blood vessel development.

 Many diseases work by affecting g-protein linked receptors.  Ex - whooping cough, botulism, cholera, some cancers

 Up to 60% of all medicines exert their effects through G-protein linked receptors.

 Extends through the cell membrane.  Intracellular part functions as a “kinase”, which transfers P from ATP to tyrosine on a substrate protein.

1. Ligand binding - causes two receptor molecules to aggregate. 2. Activation of Tyrosine-kinase parts in cytoplasm. 3. Phosphorylation of tyrosines by ATP. 4. After phophorylation, receptor protein fully activated and is recognized by specific relay proteins in cell

Fig. 11-7c Signaling molecule (ligand) Ligand-binding site  Helix Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLAS M Signaling molecule Tyr Dimer Activated relay proteins Tyr P P P P P P Cellular response 1 Cellular response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP Tyr P P P P P P

 Often activate several different pathways at once, helping regulate complicated functions such as cell division.

 Protein pores in the membrane that open or close in response to chemical signals.  Allow or block the flow of ions such as Na + or Ca 2+.

 Activated by a ligand on the extracellular side.  Causes a change in ion concentration inside the cell.  Ex - nervous system signals.

 Become activated & cause the cellular response.

 Proteins located in the cytoplasm or nucleus that receive a signal that CAN pass through the cell membrane.  Ex - steroids (hormones), NO - nitric oxide

 Activated protein turns on genes in nucleus.

Fig Hormone (testosterone) Receptor protein Plasma membrane EXTRACELLULAR FLUID DNA NUCLEUS CYTOPLASM

Fig Receptor protein Hormone (testosterone) EXTRACELLULA R FLUID Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

Fig Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

Fig Hormone (testosterone) EXTRACELLULA R FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM

Fig Hormone (testosterone) EXTRACELLULA R FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLAS M Video clip graw- hill.com/sites/ /student_vi ew0/chapter17/ani mation__intracellu lar_receptor_mode l.html

 Often has multiple steps using relay proteins such as Protein Kinases  Question #9:  amplification of signal  provide more opportunities for coordination and regulation of the cellular response

 Protein kinases transfer phosphates from ATP to protein… phosphorylation (this activates the protein)  Protein phosphatases remove the phosphates from proteins… dephosphorylation  Acts as a molecular switch

Fig Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P P PP Inactive protein kinase 3 ATP ADP Active protein kinase 3 P P PP i ATP ADP P Active protein PP P i Inactive protein Cellular response Phosphorylation cascade i

 Protein Kinases often work in a cascade with each being able to activate several molecules.  Result - from one signal, many molecules can be activated.

 Small water soluble, non-protein molecules or ions that pass on a signal.  Spread rapidly by diffusion.  Activates relay proteins.  Examples - cAMP, Ca 2+

 A form of AMP made directly from ATP by Adenylyl cyclase (enzyme)  Short lived - converted back to AMP (by Phosphodiesterase)  Activates a number of Protein Kinases which then phosphorylates various other proteins

First messenger Fig G protein Adenylyl cyclase GTP ATP cAMP Second messenger Protein kinase A G protein-coupled receptor Cellular responses hill.com/sites/ /student_ view0/chapter17/animation__secon d_messenger__camp.html

 More widely used than cAMP.  Used as a secondary messenger in both G- protein pathways and tyrosine-kinase receptor pathways.  Works because of differences in concentration between extracellular and intracellular environments. (10,000X)  Involved in muscle cell contraction and cell division

EXTRACELLULA R FLUID Fig ATP Nucleus Mitochondrion Ca 2+ pump Plasma membrane CYTOSOL Ca 2+ pump Endoplasmic reticulum (ER) Ca 2+ pump ATP Key High [Ca 2+ ] Low [Ca 2+ ]

 Secondary messenger attached to phospholipids of cell membrane.  Sent to Ca channel on the ER.  Allows flood of Ca 2+ into the cytoplasm from the ER, which activate the next protein in one or more signaling pathways  (video animation from Campbell)11_13SignalTransduction_A.swf11_13SignalTransduction_A.swf

Start here Or Start here

 #18  Cytoplasmic Regulation  Transcription Regulation in the nucleus (DNA --> RNA).

 Rearrangement of the cytoskeleton.  Opening or closing of an ion channel.  Alteration of cell metabolism.

 Activating protein synthesis for new enzymes.  Transcription control factors are often activated by a Protein Kinase.

 Enzyme cascades amplify the cell’s response  At each step, the number of activated products is much greater than in the preceding step  hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535 ::535::/sites/dl/free/ /120069/bio08.swf::Signal%20Amplification hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535 ::535::/sites/dl/free/ /120069/bio08.swf::Signal%20Amplification

 Different kinds of cells have different collections of proteins (allows cells to detect and respond to different signals)  Same signal can have different effects in cells with different proteins and pathways  Pathway branching and “cross-talk” further help the cell coordinate incoming signals

-Large relay proteins to which other relay proteins are attached -Can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway

Fig Signaling molecule Receptor Scaffolding protein Plasma membrane Three different protein kinases

 Programmed or controlled cell suicide  A cell is chopped and packaged into vesicles that are digested by scavenger cells  Prevents enzymes from leaking out of a dying cell and damaging neighboring cells

Fig µm

Fig Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- signaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Death- signaling molecule Other proteases Active Ced-4 Active Ced-3 Nucleases Activation cascade (b) Death signal

 Don’t get bogged down in details in this chapter. Use the KISS principle.  Know :  3 stages of cell signaling  examples of a receptor and how it works  protein kinases and cascades (amplification)  example of a secondary messenger