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ODSC 6A

QuestionAnswer
I. General Principles of Signaling
Signal transduction refers to the movement of signals from outside to inside
Involves ligand/receptor interaction, phosphorylation, kinases, amplification
Ligand binds to receptor, ligand gives off signal
General Idea
Slide 4Ligan/receptor interaction
Types of signaling autocrine, paracrine, endocrine
1. Autocrine molecules act on themselves
Ex IL 2 and ostepontin
2. Paracrine (proxy)act on cells nearby
3. Endocrine act on cells far away
Ex hormones
4. Synaptic signaling neurotransmitter released at the nerve terminal
II. Different types of signaling molecules or ligands
1. Hormones: Cortisol, estradiol, glucagon, insulin, testosterone, thyroid hormone
2. Growth factors: EGF, PDGF, NGF, TGF beta
3. Local mediators: Nitric oxide, Histamine
4. Extracellular matrix proteins: Collagen, Osteopontin, vitronectin, fibronectin
5. Neurotransmitters: Acetylcholine, g Aminobutyric acid
Some molecules do NOT fit into one type ex epinephrine which acts as hormone and neurotransmitter
III. How receptors relay signals via intracellular signaling
Cellular signaling cascade can follow a complex path
Receptor/ligand interaction activates intracellular proteins that amplify the signals
Steps involved in signal transduction
1. Ligand binds to receptor
2. Signal cascade transfers signals into cell
3. Cascade is continued by other intracellular molecules
4. Cascade triggers response ex; divide
Amplification of cell survival(anti apoptotic) signal by phosphorylatino and activation of akt
IV. Different classes of receptors
Extracellular receptors on surface of the cell
Intracellular receptors inside the cell in cytoplasm ex, steroids
Categories of Cell surface receptors
Types of Receptors ion, growth factor, G protein, integrin, steroid
1. Receptors with No tyrosine kinase activity have No kinases so recruit other receptors that have kinase activity
2. Receptor Tyrosine kinase have tyrosine kinase activity
Activation induces dimerization and autophosporylation which stimulates activity of intracellular kinases
3. Receptor Serine/threonine kinase Transforming growth factor
Intracellular receptors steroid receptor
1. Steroid receptor can cross plasma membrane and bind to receptors in the cytoplasm or on the nuclease
V. Intracellular proteins that act as molecular switches
Kinases mediate protein phosphorylation
Phosphatases removes the phosphate group by hydrolysis
Kinases and phosphatases act as molecular switches
Phosphorylation most common posttranslational modification and mediate protein dephosphorylation
Intrinsic enzymatic activity all can autophosphorylate, ex tyrosine kinases, tryosine phosphatases, serine/threonine
VI. Role of second messengers in the intracellular signaling
Secondary messenger refers to an intracellular signaling molecule that is downstream from the receptor
Examples of second messengers Camp, IP3, DAG, metabolites of arachidonic acid, nitric oxide
Best characterized second messengers is cAMP (cyclic AMP)
G protein largest family of cell surface receptors, secondary messenger (homodimer)
Structure polypeptide snakes through membrane 7 times
Trimeric G proteins disassemble to relay signals from G proteins
Integration of multiple pathways
Synergestic two individual signals both activate the same protein at two different sites
Converge two individual signals phosphorylate two different proteins which signals for active protein
VII. Protein, Protein interactions and modular domain
Interactions are complex interactions between signaling proteins
Mediated by modular domains
Modular domains specific/unique amino acid sequence
Common modular domains SH2 SH3 PH
Role of Modular domains mediate interaction between receptor and signaling proteins and also between signaling proteins inside the cell
VIII. Kinases and possible therapeutic targets for cancer
Fluorosis hypomineralization of teeth alters kinase and phosphatase activity
Enzymes such as kinase and phosphoratase can be used as drug targets for protein inhibitors
Bisphosphonates drugs that prevent and treat cancer induced osteoporosis by inhibiting osteoclasts
Created by: mcap
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