Cell Signaling A __________________________is a series of steps by which a signal on a cell’s surface is converted into a ________________________________________________ Signal transduction pathways convert _________________ on a cell’s surface into _____________________________ AP Biology

Signaling with _____________ Cells in a multicellular organism communicate by chemical messengers Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells In local signaling, animal cells may communicate by direct contact, or cell-cell recognition AP Biology Minzenmayer

Local vs. Long Distance Signaling Animal cells communicate using _____________________. messenger molecules that travel only short distances long-distance signaling plants and animals use chemicals called ____________________. AP Biology

Local Signaling w/o ____________________ e.g., interferon release by viral-infected cells AP Biology Minzenmayer

_______________ Signaling AP Biology Minzenmayer

Long-Distance __________ Note how specificity is determined by presence/absence of receptor protein Long-Distance __________ AP Biology

___________________________________ Often turning on or off enzyme activity In this case the receptor protein is a membrane protein Ligand AP Biology

Wrap-Up How are receptor ligand interactions similar to enzyme substrate interactions? AP Biology

Warm Up In picture A, label the following: -cell -ligand -receptor -membrane channel AP Biology

Warm Up Which diagram depicts communication between cells that are in close proximity? AP Biology

Warm Up Which diagram depicts long distance communication between cells? AP Biology

Warm Up In which type of communication would the ligand need to have the longest “life”? AP Biology

What’s the point of Cell Communication?? Examples: Epinephrine stimulates the breakdown of glycogen in mammals Temperature determines sex of some vertebrate organisms DNA repair mechanisms AP Biology

AP Biology

Receptors in Plasma Membrane three main types of membrane receptors: _______________________________________________ STEP 1: __________________________ AP Biology

____________________________________ G protein-coupled receptor plasma membrane receptor that works with the help of a G protein G protein acts as an on/off switch: If GDP is bound to the G protein, G protein is _____________________ AP Biology

_______________________ G proteins bind GTP AP Biology Minzenmayer

G-Protein-Linked Receptor Fig. 11-7b The more __________ binding, the greater the cellular response G protein-coupled receptor Plasma membrane Activated receptor Signaling molecule Inactive enzyme Enzyme GDP G protein (inactive) GDP GTP CYTOPLASM 1 2 Activated enzyme GTP GDP P i 4 Cellular response 3

Tyrosine Kinases Receptor tyrosine kinases membrane receptors that attach _________________ to tyrosines can trigger multiple signal transduction pathways at once AP Biology

Protein Kinase & Phosphatase responses tend to continue (or expand) only so long as signaling continues reversibility contributes to the dynamic nature of cells reversibility of phosphorylation makes signaling reversible AP Biology

Tyrosine Kinase Receptor Receptor dimerization Ligand Reception Protein Activation Phosphorylization Transduction Response AP Biology Minzenmayer

Ligand Gated Ion Channel ligand-gated ion channel receptor acts as gate when __________________________ changes _______________. When signal molecule binds as a ligand to receptor, gate allows specific ions, such as Na+ or Ca2+, through a channel in receptor AP Biology

Reversibility is assured by pumping ions back out again (using separate protein) Ion-Channel Receptor AP Biology Minzenmayer

Wrap-Up Would a hydrophobic molecule be expected to have an internal or membrane receptor? AP Biology

Intracellular Receptors Some receptor proteins are intracellular found in ________________ or _________________of target cells Examples of messengers steroid and thyroid _______________________ of animals An activated hormone-receptor complex can act as a _____________________________________________ turning on specific ____________________ AP Biology

____________ _________ ____________ _________ AP Biology Minzenmayer

Transduction molecules that relay a signal from receptor to response are mostly ________________________. Like falling dominoes, receptor activates another protein, which activates another, …..until protein producing response is activated At each step, signal is _____________________ into a different form, usually a __________________ change in a protein AP Biology

Protein Phosphorylation & Dephosphorylation In many pathways, signal is transmitted by cascade of protein ___________________________. Protein ____________________ transfer phosphates from ATP to protein, a process called ________________________________. Protein ____________________________ remove phosphates from proteins, a process called _____________________________. phosphorylation and dephosphorylation system acts as molecular switch, turning activities on and off AP Biology

______________________ Cascade Signaling molecule Receptor Activated relay molecule Activates protein kinase Inactive protein kinase 1 Active PK1 transfers P From ATP to inactive PK2 Active protein kinase 1 Inactive protein kinase 2 Phosphorylation cascade ATP Active protein kinase 2 ADP P PP P i Inactive protein kinase 3 ATP ADP Active protein kinase 3 P Protein phosphatases (PP) catalyze removal of P to make them inactive again PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i

Small Molecules & Ions Second Messengers extracellular signal molecule that binds to receptor is a pathway’s “___________________________________” _________________________________are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by ____________________ participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases _____________________and __________________ ions are common second messengers AP Biology

Cyclic AMP cAMP Adenylyl cyclase widely used _________________________ messengers Adenylyl cyclase converts _________________ to ________________ in response to extracellular signal AP Biology

cAMP Many signal molecules trigger formation of cAMP Other components of cAMP pathways are ________________________ G protein-coupled receptors ____________________________________ cAMP usually activates protein kinase A, which phosphorylates various other proteins Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase AP Biology

cAMP as a _____________ Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP cAMP as a _____________ ATP Second messenger cAMP cGMP acts as signaling molecule that affects relaxation of smooth muscle cells in artery walls. Compound that inhibits hydrolysis of cGMP to GMP (prolongs signal) was originally prescribed for chest pain…it increased blood flow to heart muscle…now called viagra and used to treat erectile dysrunction in males because it allows increased blood flow to penis Protein kinase A Cellular responses

Cell Signaling - Disease Cholera Caused by Vibrio cholerae in contaminated water Toxin secreted by V. cholerae in small intestine Toxin modifies ______________________involved in salt/water secretion Can no longer hydrolyze GTP Always __________________ - stimulates cAMP production Intestinal cells secrete water/ions Severe diarrhea often lethal due to dehydration and salt imbalance

Cell Signaling - Cholera Intestinal Lumen H2O, ions Ext Int GTP GDP H2O, ions Toxin active inactive Net Effect cAMP Intestinal Cell Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

Calcium Ions & Inositol Triphosphate (IP3) Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration AP Biology

Nuclear & Cytoplasmic Responses signal transduction pathway leads to __________________ of one or more cellular activities response may occur in cytoplasm or may involve action in nucleus Many signaling pathways regulate synthesis of _________________ usually by turning genes on or off in nucleus final activated molecule may function as _________________________________ AP Biology

Nuclear Response Growth factor Receptor Phosphorylation cascade Fig. 11-14 Growth factor Receptor Phosphorylation cascade CYTOPLASM Nuclear Response Inactive transcription factor Active transcription factor P DNA Gene NUCLEUS mRNA

Multistep pathways have two important benefits: Fine Tuning Response Multistep pathways have two important benefits: _________________________ signal and therefore the response Contributing to ____________________ of response Signal Amplification Enzyme cascades amplify cell’s response At each step, number of activated products is much greater than in preceding step Different cells respond differently to same chemical signal ephinephrine triggers striated muscle and liver cells to breakdown glycogen triggers cardiac muscle cells to contract (more rapid heartbeat) Why different responses from same signal? AP Biology

Signal Amplification (Cascade) AP Biology Minzenmayer

Signal Amplification (Cascade) AP Biology Minzenmayer

WRAP-UP