Local Signaling:

1. Autocrine- on cell's own surface 2. Paracrine- adjacent by secretion 3. Synaptic signaling- nerve cell releases neurotransmitter molecules into a synapse 4. Gap Junction- animals 5. Plasmodesmata signaling- plants 6. Cell-Cell recognition- direct contact between cells

Long Distance Signaling:

1. Endocrine- secrete hormones into blood to target

3 stages of cell signaling:

1. Reception- target cell detects the signal molecule when the signal molecule binds to a receptor protein located at the cells surface or receptor 2. Transduction- binding of signaling molecule changes the receptor protein. This converts the signal to a form that can bring a specific cellular response. 3. Response- the transduced signal triggers the intended cellular response.

What is the Signal Transduction Pathway?

often, transduction occurs as a series of different molecules.

What is a ligand?

Another word for signal molecule

What is a receptor protein?

What the ligand binds to

What does the ligand bind to?

The receptor binding site on the receptor protein

Where are the receptor proteins found?

In the plasma membrane and intracellular receptors(cytosol)

3 examples of cell-surface transmembrane proteins:

1. G-protein coupled receptors (GPCR) 2. Receptor Tyrosine Kinases (RTKs) 3. Ligand gated ion channel receptors

GPCR:

1. requires the use of a G protein and GDP/GTP 2. Have 7 alpha helices that span the membrane 3. Receptor activates the G protein

G protein:

1. 3 subunits- beta, gamma, alpha 2. Has a GDP bound when inactive 3. When activated, GDP is phosphorylated to GTP

What happens to the subunits when the G protein is activated?

The beta and gamma subunits are released/disassociated. The alpha subunit that is now bound to the GTP becomes an allosteric activator for an effector protein.

What is an effector protein?

The effector protein becomes the next enzyme in the pathway

RTKs:

1. Activated by autophosphorylation 2. example: insulin receptor 3. Adaptor proteins can also bind to phosphotyrosines (Tyrosine Kinase) ex: Ras

What are RTK's inactivated by?

1. Dephosphorylation 2. Internalization by endocytosis

Ligand gated ion channel receptors:

1. allows Calcium, Potassium, Chloride, and Sodium to pass through 2. very important in nervous system 3. some ion channels are controlled by electrical signals 4. often found on the membrane of the Smooth ER 5. Found on the sarcoplasma reticulum of muscle cells

Intracellular receptors:

1. Found in cytoplasm or nucleus of target cells 2. Has to pass through target cell's plasma membrane 3. Once hormone enters cell, binds to the intracellular receptor 4.The intracellular receptor turns into a hormone-receptor complex

Hormone-receptor complex:

1. deactivating specific genes 2. can also be to initiate transcription

Mitogen-Activated Protein Kinases (MAP):

1. Mitogen+ stimulated cell division by activating the normal pathways that control cell division 2. MAP kinases are activated by a phosphorylation cascade=kinase cascade 3. MAP Kinase cascades lead to signal amplification

RAS:

1. Link between the RTK and MAP Kinase cascade, small GTP binding protein 2. is active when it is bound to GTP, inactive when bound to GDP 3. A growth factor RTK activates, it activates GEF= Guanine Nucleotide Exchange Factors 4. GEF activate RAS by exchanging GDP for GTP 5. The activated RAS, then activates MKKK 6. Ras becomes inactivated when GTPase-activating protein activates the GTPase of the RAS. GTPase then exchanges the GTP for GDP

What is a Phosphorylation Cascade?

A series of different proteins in a pathway are phosphorylated. This in turn, adds a phosphate group to the next protein

What is a Kinase:

A large family of enzymes that transfer a phosphate group from an ATP to a protein.

What is Phosphatase?

Family of enzymes that remove phosphate groups

What are secondary messengers?

Small, nonprotein, water soluble molecules or ions. These readily spread through the cell via diffusion.

2 most widely used secondary messengers:

1. Cyclic AMP (cAMP) 2. Calcium

cAMP:

1. Cyclic adenosine monophosphate 2. Adenylyl cyclase converts ATP to cAMP 3. cAMP acts as an allosteric activator for enzymes in the signal transduction pathway + protein kinase A (PKA)

Calcium Ions:

1. more widely used than cAMP as second messenger 2. Ca^2+ also initiates cellular responses by binding to calmodulin 3. Increases cytosolic concentration which causes a. Muscle cell contractions b. Exocytosis of molecules c. Cell division 4. Calcium is stored in the ER 5. Releasing calcium involves Inositol Triphosphate (IP3) and Diacylglycerol (DAG)

What is Calmodulin?

1. Cytosolic protein that contains 4 binding sites for calcium 2. When 4 calcium ions bind, it then binds to other proteins a. Protein Kinases b. Ion channels c. Receptor Proteins d. Cyclic nucleotide phosphodiesterases

IP3 + DAG:

1. The enzyme phospholipase C takes PIP2 as the substrate and creates DAG + IP3 2. DAG + IP3 are allosteric activators for many enzymes 3. DAG is often an activator for PKC 4. IP3 can also be a ligand for the ligand gated ion channel receptor in the SER that releases calcium

What do many signaling pathways ultimately regulate?

protein synthesis, usually by turning specific genes on or off in the nucleus.

What is signal amplification?

At each catalytic step in the cascade, the number of activated products can be much greater than in the proceeding step.

How can different cells respond to the same cell signal yet yield a different response?

1. different kinds of cells have different proteins 2. response is dependent on its collection of signal receptor proteins, relay proteins, and proteins needed to carry out the response.

Scaffolding proteins:

large relay proteins to which several other relay proteins are attached. This increases the efficiency of signal transduction.

Termination of the signal:

1. Inactivation mechanisms are essential to any cell signaling pathway 2. for a cell to remain capable of responding to incoming signals, each signal pathway must last only for a short time. 3. The ability of a cell to receive new signals depends on the reversibility of the changes produced by prior signals.

What is Apoptosis?

1. Programmed cell death 2. cellular agents chop up the DNA and organelles 3. occurs when a cell is damaged or old.