Cell Signalling and Cell Cycle Flashcards

Flashcards about Cell Signaling and Cell Cycle

Why do cells need to coordinate their behavior?

Growth and development, fighting disease and pathogens, movement, functioning of nerve impulses, processing and storing nutrients, controlling behavior

What is a ligand?

Signaling molecule that binds to a receptor.

What can ligands be made of?

Small proteins, peptides, molecules, or dissolved gasses (e.g. steroids, neurotransmitters, testosterone)

Why do signal molecules have different effects on different target cells?

Different receptors, different intracellular signaling proteins, and different effector proteins.

Name the two domains of cell-surface receptor proteins

Extracellular, intracellular.

How do ion channel-coupled receptors work?

Ligand binding causes a confirmational change, which can open or close a pore.

Name the two kinds of 'switches' involved in cell signaling.

Kinases (phosphorylation) and G proteins (GTP binding).

How do kinases work?

Protein kinase uses ATP and adds P to inactive protein which in turn activates the protein to pass the signal. Protein phosphatases (removes P) and turns protein off.

How does G-protein work?

GDP bound protein is OFF. Signal comes in, GDP removed and GTP added. Only if GEF activates G protein

What are second messengers?

Small molecules that can convey signals through the cell. They amplify the signal, activate multiple pathways, and create a rapid response.

Give examples of second messengers.

Ca2+, cAMP (made by the enzyme adenyl cyclase from ATP), and diacylglycerol.

What do enzyme-coupled receptors do?

Function as enzymes or with enzymes that they activate.

What are mitogens?

Signaling molecules which stimulate cells to divide.

What are mitogen activated pathways?

Receptor tyrosine kinases (RTKs) - phosphorylate tyrosine.

How are RTKs activated?

Trans-autophosphorylation (brings 2 parts together to phosphorylate) and then act as docking site for other signalling proteins.

What is Ras?

G-protein anchored in the plasma membrane. Active state; GTP bound turned on, only if GEF activates G protein

How do adaptor proteins on receptors bring everything together?

Binds through SH2 domain (by recognizing 1 phospho-tyrosine).

What are GPCRs?

Is a G-protein-coupled receptors and indirectly regulate the activity of separate-bound enzyme.

Name the three domains of a G protein.

Alpha, beta, and gamma.

What is the basic structure of G-protein coupled receptors?

G-protein coupled receptors have the same basic structure; single polypeptide chain w/ 7 transmembrane helices

Adrenaline pathway activates what?

Activated G protein alpha activates adenyl cyclase (ATP to cAMP)

In adrenaline pathway PKA switches what on and off?

Glycogen breakdown is switched ON and glycogen synthesis is switched OFF

How does GPCR pathway work?

Ligand binds to GPCR, then GPCR confirmational change, which activates G protein trimeric GTP-binding protein. Alpha subunit releases bound GDP and GTP becomes bound. GTP bound leads to confirmational change so alpha dissociates from beta, gamma complex

What are the phases of cell division in eukaryotes?

Interphase, prophase, metaphase, anaphase, telophase.

What are the subphases of interphase?

G1, S, and G2.

What are the checkpoints in the cell cycle?

G1 to S (start), G2 to M (enter mitosis), and metaphase to anaphase (MZA).

Reasons why cells divide?

Development, replacement/renewal/repair, and reproduction.

What is Cancer?

Uncontrolled cell division

What are solutions to studying the cell cycle regulation, where cells do not go through the cycle at the same time?

Study natural occurring synchronized cells, manipulate cell cultures; or cell cycle mutants.

What are cyclins?

Proteins that are made and destroyed during the cell cycle.

What causes changes in Cdk activity (not Cdk conc)?

Combination of cyclin and CDK at different phases of the cell cycle.

What happens during G1 phase with G1 and G1/S phase cyclins?

Are present and active early in the cell cycle and initiate entry into S phase

What happens during S phase in S-Cdks?

Activate unwinding of DNA and initiate DNA replication in S phase.

What do M-Cdks do?

Trigger chromosome condensation, induce assembly of the mitotic spindle, and ensure correct chromosome attachment to the spindle (drive entry into mitosis).

What happens when Cyclin partly activates Cdk?

Cyclin partly activate Cdk. When cyclin binds, ATP loops are pulled to open up to phosphorylate. Cyclin levels are controlled through txn, tln, and degradation to control cyclin levels.

What do CAKs do?

Fully activate Cdk.

How does the P27 inhibitor inhibit in cell cycle?

P27 warps around compelx and blocks substrate from getting into active site -> inactive

Wee1 and Cdc25 phosphatase do what in the cell cycle?

Wee1 phosphorylates Cdk-cyclin complex to inactivate. Cdc25 phosphatase removes P group - activates Cdk-cyclin complex

What is the purpose of S-Cdks?

Activates DNA replication.

What happens during Active M-Cdks Early Mitosis?

Active M-Cdks phosphorylate target proteins to trigger events of prophase. They activate condensins and phosphorylate lamins thus membrane destabilizes.

What is APC/C (anaphase promoting complex)?

Regulates late mitosis. Flags proteins w/ ubiquitin (signal protein to be degraded).

Give an example of how Ubiquitin is used

M cyclin can be flagged w/ ubiquitin to promote anaphase (separation of chromatids)

How does APC/C trigger Metaphase to anaphase transition?

Flags securin with ubiquitin to degrade securin, which is attached to separase therefore separase is free so can cut cohesions thus the 2 chromosomes separate for anaphase .

What are Mitogens?

Extracellular signals that trigger cell divisions. e.g Platelet-derived growth factor (PDGF) released from platelets at blood clots which help stimulate cell division during wound healing

What are the 4 steps of Mitogens stimulating cell cycle

1. Act through signaling cascade (using MAP kinase)

2. Mitogen activates Myc gene → activating G1 cyclin

3. G1 Cyclin forms w/ G-Cdks → activates E2F → turns on G1/S cyclin and S cyclin

4. G1-Cdks lift repression of E2F (phosphorate and deactivates Rb)

Mutated Rb protein will cause?

Mutated Rb protein will always have E2F active which equals a cell cycle always on and loss of control

Rat Sarcoma - RAS, is it similar or opposite to Rb?

Opposite to Rb. Active means it promotes cell cycle

What controls a cell cycle?

Cyclins control the cell cycle, but mitogens and environment determine if cyclin expressed

What does a Restrictive condition means?

High Temperatures, mutated protein causes denaturation. Cell cycle always blocked at same stage and the mutated gene acts at (or prior) to that point in division

Species used where fertilisation is external for cell cycle research?

African clawed frog & Sea Urchin embryos

What is the DNA Checkpoint Cycle I to repair any mutations?

1.ATM/ATR kinases activates when DSB (radiation) 2.Active ATM/ATR activates Chk1/Ch2 kinase 3.Activates p53 (Guardian of the Genome)- blocks cell cycle and DNA repaired 4.P53 activates p21 5.Activated p53 binds p21 gene - encodes for CKI (inhibitor) and then 6.CKI inactivates cyclins and blocks cell cycle