Cell and Molecular Biology Exam 4

Types of extracellular signaling molecules

• Proteins, peptides, amino acids, gases, nucleotides, steroids, fatty acids

3 Classic end results of signal transduction

1. Metabolic enzyme

2. Alter cell shape or movement

3. Alter gene expression

Types of extracellular signaling molecules

• Proteins, peptides, amino acids, gases, nucleotides, steroids, fatty acids

3 Classic end results of signal transduction

1. Metabolic enzyme

2. Alter cell shape or movement

3. Alter gene expression

Exceptions to the 3 classic end results of signal transduction

1. Steroid hormones

2. Gases as signals

Nitric oxide is synthesized from

argenine

Nitric oxides (exception 2 gases as signals)

• Nitroglycerine (relax heart muscles b.v. dilation)

• Viagra (NO released from nerve terminals)

  • block degradation of cyclic GMP

Formation of nitric oxide in endothelium

IP3→Ca+ (activated NOS)

Arg-(activated NOS)→ Nitric Oxide

Goes across membrane to smooth muscle cell and affects

Guanyl cyclase

GTP activates cyclic GMP (rapid smooth muscle relax)

Steroid Hormones

cortisol, estradiol, testosterone, thyroid H

• Hydrophobic molecules that trans the PM

Protein kinase (molecular switch)

• covalent addition of P group

• does not always activate

• some only add to specific residues

  • Tyr. kinase: P Tyr.

Phosphatases (molecular switch)

remove P

GTP binding protein (molecular switch)

GTP→GDP (thru GTP hydrolysis)

Ion channeled couple receptor

Ion channel with receptor (opens with correct signal)

• Neurology (NT binds to receptor and opens it)

  • K+, Na+, Ca+ flows

G-Protein Coupled Receptor steps

1. EC signal

2. GPCR binds to receptor

3. Conformational change in receptor

4. G protein activates

cyclic AMP is activated by

GTP

Cyclic AMP activates

PKA

Active PKA activates

• Phosphorylated transcription regulator

  • transcription of target gene

• Phosphorylated kinase

  • active glycogen phosphorylase

  • glycogen breakdown

Adenyl Cyclase

1. produce cAMP and phospholipase C

2. Produce inositol triphosphate (IP3) and diacyl glycerol (DAG)

3. signal for accumulation of intracellular Ca+

Adenyl cyclase cycle

1. Phospholipase C

2. PI 4,5 biphosphate

   • IP3 opens calcium channel

3. DAG

4. Protein Kinase C (active when Ca+ binds)

Ca + Response proteins

1. Calmodulin: cytosol; binds Ca+ and conformationally changes

2. Ca+ Calmodulin Dependent protein kinases (CAM kinase)

   • neuronal synapses in memory

   • P things

Ligand binding domain is on the

extracellular side

Enzyme binding domain is on the

intracellular side

• substitute for G protein

RTKs pass the plasma membrane

one time using a single alpha helix

Activated RTK form

dimer with activated kinase domains P

• occurs on Tyrosine residues

Ras GEF

GDP→GTP

• Ras GTP is active form

RTK Grb2

Adaptor protein (scaffolding/support)

• SH2 domain grabs RTK

• SH3 domains: scaffold for SOS

• SOS:GEF for Ras

Active RAS produces

1. MAP Kinase, Kinase, Kinase (Raf)

2. MAP Kinase, Kinase (Mek)

3. MAP Kinase (Erk)

   1. Changes protein activity

   2. Chane gene expression in the nucleus

How to stop RTK signal

• Protein tyrosine phosphatases

  • Remove P off of RTK

    • Endocytosis of RTK

      1. Lysosome and is degraded

      2. Recycles back to PM

• Ras GAP→ GTP to GDP (hydrolysis)

• Phosphatases for all MAP Ks

P!-3 Kinase

• P specific lipids called inositol proteins

  • serve as docking sites for intracellular signaling proteins

PI-3: AKT signaling pathway

relocated to PM; Ser/Thr kinase (protein kinase B)

Protein Kinase B (Ser/Thr kinase)

promote cell growth and survival through P

• P protein Bad

  • inactivates Bad

    • active bad normally promotes cell suicide; inactivation of Bad discourages cell suicide

  • Activate Tor: important for cell growth

Rapamycin

inactivates Tor

• anti-cancer drug

3 major classes of macromolecules in CT

1. GAGs

2. Collagen

3. Non-collagen glycoproteins

   • carry traditional asparagine linked sugar (oligosacchride)

There are __ different collagen genes

20

Proteinase (secreted procollagen)

• weaker connective tissue

• decrease tensile strength

• collagen fibrils don’t assemble correctly

Non-collagen proteins (macromolecule of CT)

1. Elastin: elastic fibers

   • recoil after transient stretch

2. Fibronectin: ECM protein secreted by fibroblasts

   • linkage to epithelial cells

Glycosaminoglycans

GAGs

• negatively charge polysaccharide chain

  • repeating disaccharide units

• covalently link to core proteins

• have many GAG sidechains attach to single core protein (aggregation)

• Hyaluronan (simplest GAG form)→ healing

Cells attach to the

ECM side of the basement membrane

Cell fxns in the super basal end are

different of those at the basal level

Two types of integrin complexes

1. Hemidesmosome: intermediate filament (cell) and laminin (BM)

2. Focal Adhesion: actin (cell) and ECM proteins (BM)

How many types of integrins are there

24

• each type specific to ECM protein

Integrin helps cell crawl

Leukocyte Adhesion deficiency: lack integrin that help WBC crawl out of blood vessel so it cannot get to site of infection

Adaptor proteins in cell matrix junction

• Talin

• Vinculin

• Kindlin

Alpha integrin attaches to

focal adhesions and actin cytoskeletons in the cell

Basal lamina

CT, thin ECM, collagen IV and laminin (similar to fibronectin)

Cadherins attach to cytoskeleton

actin and intermediate filament on the inside of cell

• Homophilic binding: if linkage is to actin on both sides

Cell-Cell Junctions

1. Adherins (actin)

2. Desmosomes (intermediate filaments)

Cell-matrix junctions

1. Focal adhesions (actin)

2. Hemidesmosomes (intermediate filaments)

Adherins (Cell-Cell jxn) → actin

• Cadherin (E, P, N)

• Adaptor proteins

  • (B, p120, alpha, vinculin catenin)

• Actin

• Adhesion belt (corticol actin)-. below tight jxn

Desmosomes (Cell-cell jxn)→ int filaments

• Cadherin

  • Desmoglein (I-IV)

  • Desmocollin (I-III)

• Adaptor proteins

  • plakoglobin

  • plakophilin

  • desmoplakin (int filaments)

Tight junction proteins

1. Occludin

2. Claudin

water soluble molecules cannot pass through

Transcellular transport happens if

tight jxn is too tight (cannot pass through)

• transport proteins in PM and again on basal surface for release into blood vessel

Communicating junction (GAP junction)

• Connexons: narrow, water-filled channel

  • homomeric and heteromeric

• Electric and metabolic coupling between cells

EMT- Epithelial Messenchymal Transition

• Epithelial: established and adherent

• Messenchymal: unattached and change shape and migrate

Super basal cells are

not able to be differentiated or undergo mitosis