Signal transduction Flashcards
What are the types of cell to cell communication
Endocrine, paracrine, neuronal, contact dep, autocrine
Describe the general signal pathway of comm
Sig (ligand) - R - secondary msgr and intracell sig molec - target prot - Response
Lig-R can initiate specific or mutli cell reponses
What are the intracell signal proteins
- Kinases (tyrosine kinase, serine/threonine kinase)
- GTP-binding prot (G prot)
Act as molecular switches = Phos/on
What are the cell surface receptors involved in signal transduction
G-prot coupled R - Androgenic and olfact
R-Tyrosine kinase (RTK) - GFRs and insulin-R
Serine/Threonine KR - TGFB-R
Receptors w/o k act - Cytokine R, integrins
Ion-channel linked R - Neurotrans
What are the intracell receptors involved in sig trans
Steroid hormone
What are the classes of MembR
- Ligand bound op/close channel
- Ligand binding to receptor enzyme activating intracell enzyme
- Lig to G prot opens ion channel or alters enzyme act
- Lig - integrin altering cytokines
Describe GPCR pathway
- L-R; G-R, L changes conform - G activation
- GDP on alpha-subunit displaced with GTP
- Heterotrimeric G breaks to alpha and betagamma each anchored to PM, exposes sites to bind effectors
- alpha or betagamma interact with effector, moding activity
- alpha has GTPase activity (Hydro GTP to GDP)
- At GDP alpha, G prot reassociates ending signal
Secondary messengers are: cAMP (eff=adenyl cyclase) IP3/ DAG (eff - phospholase C; PLC)
Describe GPCRs interaction using cAMP
- L to G prot-R therefore activating G
- G turns on adenyl cyclase increasing enzyme
- Adenyl cyclase converts ATP and cAMP
- cAMP activates PKA (Ser/Thr K)
- PKA phos other proteins leading to cell response
- PKA catalytic subunits also enter nuc to phos (act) TF: CREB to CRE (cAMP R Enzyme) in promoter region of cAMP response genes
- cAMP phosphodiesterase converts cAMP to 5’AMP turning off signal (inhib by caffeine)
- Heterotrimeric G prot and alpha = stim (Gs) or inhib (Gi)
Describe GPCRs with DAP and IP3
Eff prot = PLC which breaks down PL to secondary messengers
1. Inositol-triphes (IP3) increases Ca which binds to Ca binding proteins activating PKC which activate TFs
2. Diacylglycerol (DAG) acts PKC which activates TFs
PKC is a ser/thr kinase C
Describe RTKs
Transmembrane with TK activity = Growth Factor and Insulin receptor. Catalytic receptors activated by dimerization.
L- Recep dimer - tyrosine phos - kinase act - phos effector
Activated RTK effector proteins
- PLC to inositol to 2nd msgrs IP3 and DAG
2. PI3K - phos membrane PLs products - act PKB - cell proliferation and growth - inhibt apoptosis
RTK effector proteins and revealing of docking site = GRB2
GRB2 binds SOS (GEF) - act small G (RAS) - act mitogen activated PK (MAPK) pathway - TFs (FOS and JUN) - produces GF3, GFRs, cell cycle proteins
Describe specific GRB2 path
R Phos - recruits adapt proteins. GRB2 binds pTyr (SH2) and SOS (via SH2) to substrate (Ras). SOS = guanine exchange factor (GEF). Ras=GTPase/G-prot. GAP=off GEF=on
Describe RTK insulin receptor
R-monomers linked by S-S auto phos tyr residues. Use GRB2, SOS, Ras mediates and stim transC
Ins signal also functions in cytosol to alter meta activity and fusing vesicles with glucose transporter (GLVT) to PM -> glucose uptake
Describe Cytokine receptor
Similar to RTK w/o TK, Lig=ILs, G-CSF, GF. Activates kinase domains on proteins (JAK). JAK/STAT path enabled (sig transducers and activation of transC)
