GENERAL SIGNALING STEPS 1.

Cells interact with their environment by interpreting extracellular signals via proteins that span their plasma membrane called receptors 2. Receptors are comprised of extracellular and intracellular domains 3. The extracellular domain relays information about the outside world to the intracellular domain 4. The intracellular domain then interacts with other intracellular signaling proteins 5. These intracellular signaling proteins further relay the message to one or more effector proteins 6. Effector proteins mediate the appropriate response

Transmitting the Signal: Protein Kinases Activated receptors frequently transmit signals through through

intracellular signaling proteins called kinases Protein kinases are enzymes that add a phosphate group from ATP onto a substrate protein; this reaction is called phosphorylation Phosphorylation frequently serves to activate the substrate of the kinase, but can also target the substrate for degradation Kinases are often themselves activated by other kinases via

phosphorylation and can organize into phosphorylation cascades One important class of phosphorylation cascade is called a mitogen activated protein kinase (MAPK) cascade IMPORTANT FEATURES OF SIGNAL TRANSDUCTION 1. SPECIFICITY Signal molecule (S1) fits binding site on its complementary receptor; other signals (S2) do not fit Specificity is achieved by precise molecular complementarity between the signal and receptor molecules mediated by the same kinds of weak (noncovalent) forces that mediate enzyme-substrate and antigen-antibody interactions.

Multicellular organisms have an additional level of specificity, because the receptors for a given signal, or the intracellular targets of a given signal pathway, are present only in certain cell types.

Thyrotropin-releasing hormone, for example, triggers responses in the cells of the anterior pituitary but not in hepatocytes, which lack receptors for this hormone.

Epinephrine alters glycogen metabolism in hepatocytes but not in erythrocytes; in this case, both cell types have receptors for the hormone, but whereas hepatocytes contain glycogen and the glycogen-metabolizing enzyme that is stimulated by epinephrine, erythrocytes contain neither.

2. AMPLIFICATION When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade. Amplification by enzyme cascades results when an enzyme associated with a signal receptor is activated and, in turn, catalyzes the activation of many molecules of a second enzyme, each of which activates many molecules of a third enzyme, and so on. Such cascades can produce amplifications ofseveral orders of magnitude within milliseconds.

3. DESENSITIZATION/ADAPTATION Receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface. The sensitivity of receptor systems is subject to modification. when a signal is present continuously desensitization of the receptor system results when the stimulus falls below a certain thresh-old, the system again becomes sensitive. 4. INTEGRATION A final noteworthy feature of signal-transducing systems is integration

 The ability of the system to receive multiple signals and produce a unified response appropriate to the needs of the cell or organism. Different signaling pathways converse with each other at several levels, generating a wealth of interactions that maintain homeostasis in the cell and the organism.

BASIC SIGNALING MECHANISMS 1. Gated ion channels of the plasma membrane that open and close (hence the term gating) in response to the binding of chemical ligands or changes in transmembrane potential. These are the simplest signal transducers. The acetylcholine receptor ion channel is an example of this mechanism 2. Receptor enzymes, plasma membrane receptors that are also enzymes. When one of these receptors is activated by its extracellular ligand, it catalyzes the production of an intracellular second messenger. An example is the insulin receptor 3. Receptor proteins (serpentine receptors) that indirectly activate (through GTP-binding proteins, or G proteins) enzymes that generate intracellular second messengers. This is illustrated by the -adrenergic receptor system that detects epinephrine (adrenaline) 4. Nuclear receptors (steroid receptors) that, when bound to their specific ligand (such as the hormone estrogen), alter the rate at which specific genes are transcribed and translated into cellular proteins. Because steroid hormones function through mechanisms intimately related to the regulation of gene expression 5. Receptors that lack enzymatic activity but attract and activate cytoplasmic enzymes that act on downstream proteins, either by directly converting them to gene-regulating proteins or by activating a cascade of enzymes that finally activates a gene regulator. The JAK-STAT system exemplifies the first mechanism ; and the TLR4 (Toll) signaling system in humans, the second

6. Receptors (adhesion receptors) that interact with macromolecular components of the extracellular matrix (such as collagen) and convey to the cytoskeletal system instructions on cell migration or adherence to the matrix. Integrins illustrate this general type of transduction mechanism.

FUNCTIONS OF PHEROMONES Communication Health and Fitness Mate Choice/ Sexual Selection Mate Selection to Avoid Incest/Genetic Relatedness Sexual Maturation Successful Fertilization (Aquatic Animals) Kin Recognition Caste and Reproductive Status (Social Animals) Menstrual Synchrony Maternal-Infant Bonding Infant SucklingNipple Recognition Dominance Hierarchy Aggression Territory and Trail Marking Deception (Plant->Animal) Deception (Animal->Animal) Aggregation Intruder Alarm

PHEROMONE IN APPLICATION CIA used cockroach sex pheromone to capture/identify spy Perfume industry Cat pheromone used by cats and other felides for cat communication. Feline facial pheromone: A hypothetical pheromone used by cats to mark places, objects, and persons as familiar by rubbing their face on surfaces. It is currently not known if there actually exists a "feline facial pheromone" and what its chemical structure is.

Feliway(trademark):A preparation that claims to contain or to mimic the feline facial pheromone is commercially available under the name Feliway Cat attractants A domestic cat demonstrating the effects of catnip such as rolling, pawing, and frisking Cat attractants are odorants and constituents of essential oils that have an apparent effect on cat behaviors A cat presented with a cat attractant may roll in it, paw at it, or chew on the source of the smell. The effect is usually relatively short, lasting for only a few minutes after which the cats have a refractory period during which the response cannot be elicited. After 30 minutes to two hours, susceptible cats gain interest again. These compounds might mimic the feline facial pheromone. The volatile chemicals that are currently known to cause these behavioral effects in cats are actinidines from Valeriana officinalis, nepetalactone from Nepeta (catnip), dihydronepetalactone, neonepetalactone,

isodihydronepetalactone, epinepetalactone, boschnialactone, boschniakine, dihydroactinidiolide, actinidiolide, iridomyrmecin, (-)-

mitsugashiwalactone, and onikulactone INSECT MONITORING PHEROMONE TRAP

MOLECULAR EVEN OF OLFACTORY 1. Sensory neurone cillia is submerged in mucus layer. Odorant molecule dissolved in the muccus and 2. Bound to a 7-pass transmembrane protein receptor within cillia 3. Activate G protein of the receptor (at the sitoplasm site) 4. Active G protein then activate adenylil cyclase at the plasma membrane of cillia 5. Active adenylil cyclase catayze the convertion of ATP to cAMP within cytosol 6. cAMP open ligand-gated (cAMP gated) sodium channels Na+ influx 7. Na+ influx lower plasma membrane potential (depolarization)

8. When depolarization reaching threshold 9. Action potential proceed 10. Action potential continue and transmitted along the olfactory nerve to the brain 11. Brain respone to the olfactory signal and processed to become smell perception