Cellular Signaling Section 2-3

Discussion Points: What happened? How did you recognize where to go? How does this model cell communication? What effect did joining the pathway have on you? (Looking for something to indicate conformational change.) What problems did you encounter? What would have happened if someone didn’t do their job (follow instructions) or weren’t there?

Notes Quiz: 1.List the three general steps to cellular signaling. 2.Define Ligand. 3.Describe phosphorylation. 4.What is a protein kinase.

Two Kinds of Cell Signaling Local Regulators Secreted by the signaling cell influence cells in close proximity Hormones Long distance signaling; they travel through the blood stream of humans also known as endocrine signaling because hormones are secreted by special structure called endocrine glands

Reception- the detection by a target cell of a signaling molecule; occurs when a signal binds to a receptor protein on the pm of the target cell Transduction- the binding of the signal changes the protein in some way (think change in shape, change in function) Can be single step, or a signal transduction pathway changes in a series of different molecules Response- any cellular activity!!!

Reception

General Process Signal molecule is complimentary in shape to a site on the receptor Ligand- general term for a molecule that binds specifically to another larger molecule Causes the receptor protein to undergo a change in shape causing a change in function

Intracellular receptors Inside Cell-cytoplasm or nucleus Signal must be hydrophobic enough and small enough Often receptor also carries out transduction All very similar in structure suggesting an evolutionary relationship Examples: steroid hormones and thyroid hormones

Membrane Receptors Transmembrane proteins Transmit information from extracellular environment to intracellular environment by changing shape when ligand binds

G-protein Linked Receptor Structure outside area for a signal to bind Inside area where a G-protein binds

G-protein Linked Receptor Function G protein linked receptor receives the signal activated receptor binds the G-protein exchanging GTP (energy, activating) for GDP G protein diffuses along the membrane and binds an enzyme, allosterically activating it; the enzyme triggers the next step in the pathway when the signal molecule is released the G protein will replace GTP with GDP deactivating itself and restoring the resting state

G-Protein-Linked Receptor Key Feature: ability to turn off quickly Where/When Used: embryonic development and sensory reception Diseases: cholera, pertussis, botulism

Receptor Tyrosine Kinase Kinase- general term for an enzyme that phosphorylates another protein Structure Two subunits with two signal-binding sites outside the membrane span the membrane three typrosine aa’s on each separated= inactive, together= active

Receptor Tyrosine Kinase Function Signal binds two subunits connect with each other forming a dimer once bound together, the two protein subunits phosphorylate each other once activated, the proteins are recognized by relay proteins to trigger a cellular response

Receptor Tyrosine Kinase When/Where used: cellular growth and reproduction Key Feature: because there are six activated binding sites, it can trigger a quick massive cellular response by activating multiple signal transduction pathways Diseases: cancer

Ligand gated ion channels Structure- a closed ion channel when inactive, an open one when active Function Signal molecule binds gate opens ions flow through causing a cellular response when the ligand dissociates, the gate closes When/where used: nervous system signaling

Transduction

Phosphorylation and Dephosphorylation Protein kinase- protein that transfers phosphate to another protein Act on proteins other than themselves Often act on other protein kinases Phosphorylation cascade- a series of protein kinases one acting on the next

Protein phosphatase- enzyme that rapidly removes phosphates from proteins Turns activated proteins off Makes proteins available for reuse

Secondary Messenger small water soluble molecules involved in transducing a signal

cAMP Receptor protein activates a G-protein G-protein activates an enzyme that turns ATP into cAMP cAMP activates protein kinase Protein kinase induces a response Important pathway in the regulation of water/salt balance in intestines

Calcium ions High concentration found outside cell and inside ER (when compared to cytoplasm) Signal at membrane causes release of calcium from ER Leads to a cellular response Important pathway in muscle contraction

Response

Enzyme activation- binding to an enzyme changes its shape and function Transcription factors- activate transcription of specific gene

Why so Many Steps Signal Amplification- each step of the pathway activates more proteins than the last leading to a larger response Specificity of Signaling Most signals are cell specific Some can work on multiple cells but induce a different response in each