Signal Transduction

• Reception
• Transduction
• Response

• 1. Synthesis of molecule
• 2. Release of molecule
• 3. Secretion
• 4. Binding receptor
• 5. Activation of signal transduction machinery
• 6. Change in gene expression
• 7. Termination of cellular response
• 8. Elimination of Signal molecule

• 1. Pineal
• 2. Pituitary
• 3. Thyroid
• 4. Thymus
• 5. Testes
• 6. Ovaries
• 7. Adrenal Gland
• 8. Pancreas

• cAMP - Protien Kinase A
• cGMP - Protien Kinase G + cation channels in rod cells
• DAG - Protien Kinase C
• IP₃ - Opens Ca²⁺ channels in ER

• Cytosolic multipurpose switch protien that mediates the effects of Ca ions.
• Calmodulin activation of Calcinuerin which is a protien phosphatase that activates Il-2
• Il-2 stimulates t-proliferation

• Immunosuppressant drug
• Forming a complex with cyclophilin which inhibits calcineurin
• Knocks down immune sys by preventing Il-2 release/activation

• 1. cAMP reception activates G-prot
• 2. G- prot activates Adenylate cyclase
• 3. cAMP diffuses out of cell into media
• 4. Internal cAMP inactivates external receptor
• 5. Another G-prot stimulates Phospholipase C
• 6. IP₃ induces Ca²⁺ release
• 7. Ca²⁺ induces extension of psuedopodia

• 7 transmembrane alpha helices with 4 extracellular loops and 4 intracellular loops.
• Loops 3 and 4 (sometimes 2) interact with G-prot.

cAMP

IP₃ and DAG

cGMP

• Effector protien to G-protien
• IP₃ and DAG

secondary messnagers that act on Ca²⁺ Channels (IP₃) and activate Protien Kinase C (DAG) which phosphorylates various enzymes and receptors, altering thier activity.

Growth factor that stimulates differentiation in hematopoietic stem cells specifially in Colony Forming Units which are erythroid progenitor cells

Inducing trx of anti-apoptotic factors allowing the cells to RBC's

Epo (ligand) --> EpoR --> JAK --> STAT, Ras/MAP, Phospholipase C, and PI₃ Kinase which lead to trx activation.

Homodimer with extracellualr ligand receptor irreversably connected to cytosolic JAK prot which is activated by dimerizing after ligand binds receptor. This causes the the JAK kinases to phosphorylate eachother on a Tyr residue at the activation lip. This increases the ability of ATP to bind and subsequent Tyr residues are phosphoylated creating docking sites for the inactive STAT monomers (trx factor - dimerizes with another STAT prot once phosphorylated = active)

RTK = Different monomers which form heterodimers or homodimers when bound by a ligand. The ligand induces a loop in the cytosolic domain which interacts with the other RTK activating a protein similiar to JAK (only this is part of Cytokine)

• HER
• 4 which differentially bind to various EGF

It is in a preactivated state and can form heterodimers with HER 1, 3, and 4. HER3 can only signal when bound to HER2 (lacks functional kinase domain)

HER2 make the cell sensitive to low levels of any factor of the EGF family. Levels that would not stimulate growth with normal HER2 levels.

• Cetuximab
• inhibiting RTK

• Herceptin
• Breast Cancer
• specific
• Extracellular

Ras is monomeric

• RTK binds ligand and dimerizes phosphorylating cytosolic tyrosine residue
• GRB2 (comprised of SH2 and SH3) binds Sos (SH3 specically binds Sos)
• Sos binds inactive Ras causing GDP to dissociate and GTP to bind

• Ras is activated
• Recruits and binds/activates Raf - Raf is activated because the 14-3-3 protein that stabalizes Raf in its inactive form is dephosphorylated
• Hydrolysis of the Ras GTP --> GDP releases the active Raf from Ras
• Raf phosphoryaltes MEK's activation lip
• MEK phosphoylates MAP kinases activation lip
• MAP kinase dimerizes and translocates to nucleus
• MAP kinase phosphorylates many different prot. including nuclear trx factors

• It is activated via Ras-Raf
• Dimerizes in cytosol
• activates p90^RSK by phosphorylating its activation lip
• MAP kinase and p90^RSK both then move to nucleus
• p90^RSK phosphorylates/activates SRF (a trx factor)
• Nuclear MAP kinase phosphorylates/activates TCF (trx factor)
• TCF and SRF act together to stimulate trx of genes that contain SRE (enhancer region upstream of gene coding sequence) in thier promoter

Scaffolding Protein: large relay proteins to which other relay proteins are attached (increase signalling transduction efficiency) -groups together different proteins in pathway

A rare x-linked recessive disease that creates a missense mutation in WASP (Wiskott-Aldrich Syndrom Protein - Prot expressed in hematopoietic cells involved in signal transduction)

• Receptor Dephosphoylation
• Receptor Degredation
• Receptor Endocytosis

SHP1 is a heterodimer with SHP2 which binds phosphorylated tyrosine resdues on cell receptor. This activates the phosphotase on SHP1 which dephosphorylates the JAK activation lip

• STAT pathway induces SOCS protein
• SOCS binds phosphotyrosines on JAK and blocks other SH2 molecules - also ubiquinates it for degredation via the proteosomal pathway