Cellular Signaling Lecture - Coggle Diagram
Cellular Signaling Lecture
GPCR acts as a GEF; activates alpha subuint of G-protein; alpha then dissociates from beta and gamma units to go activate targets.
Signal amplification occurs w/ second messenger
2nd Messenger: Adenyly cyclase - cAMP
cAMP targets protein kinase A (PKA), gated ion channels, and/or exchange protein activated by cAMP (EPAC)
Through PKA (serine/threonine kinase), CFTR increases Cl- transport and MLCK for smooth muscle relaxation.
A kinase anchoring proteins (AKAPs) are scaffolds, promoting specificity.
PKA can phosphorylate cAMP response element binding protein (CREB) to active CRE to activate transcription
CRE acts in long-term changes like learning and memory.
Inactivation: Phosphodiesterase (PDE)
Phosphodiesterase inhibitors increase cAMP by preventing its degradation
G(alpha) s stimulates cAMP; G(alpha)i inhibits cAMP
2nd Messenger: Phospholipase C- (PLC Beta),Diacylglycerol (DAG), IP3, Ca2+
PLC beta activated by Gq protein. Activation of PLC B cleaves PIP2 to IP3 and DAG.
DAG serves as a receptor of sorts on protein kinase C on the PM.
Protein Kinase C is involved in inhibiting the insulin signaling that recruits Glut4 channels to the membrane for glucose intake.
IP3 binds to an ER receptor, releasing calcium
Protein: Calmodulin (CaM) will bind to released calcium and activate CaM kinase
Kinase activates myosin light chain kinase (MLCK) for contractions
1 more item...
Target: Ion channel
Effect: Change in PM permeability
Toxins alter cAMP signaling by modifying G(alpha)i
Inhibits G(alpha)s; increases cAMP
Inactivates G(alpha)i. Prevents cAMP inhibition; increased cAMP.
Regulator of G-protein signaling (RGS) acts as GAPs.
Use of GAPs cause re-association of subunits that dissociated as a result of activation.
Enzyme Coupled Receptors
Serine/threonine kinase: TGF Beta receptor
Regulates proliferation and ECM deposition
TGFB binds to its type 2 receptor. Results in recruitment and phosphorylation of type 1 heterodimer
Type 1 phosphorylates Smad2/3. Smad2/3 then dissociate and go bind to Smad4
Smad4 translocates to nucleus to regulate gene transcription.
Disease: Interstitial pulmonary fibrosis - TGF beta drives myofibroblast proliferation and collagen disposition
These sort of receptors dimerize w/ activation and has enzymatic activity due to being coupled or intrinsically.
Receptor Tyrosine kinases (RTKs)
Activation results in dimerization
Promotes trans-autophosphorylation where each part of the receptor polypeptides phosphorylates the others
Proteins downstream w/ SH2 domain lik Grb2 binds to activated RTK.
Drug: Imatinib used to treat leukemia and some GI tumors.
Grb2 recruits Ras-GEF, activating Ras.
Ras activates and activates MEK. MEK activates MAPK (Erk)
Erk can phosphorylates protein in cytosol or go to the nucleus and alter gene expression via phosphorylation of gene regulatory proteins.
Tyrosine kinase-associated receptors: JAK or Janus kinases
RTK recruits STAT proteins via SH2 domain.
STAT phosphorylated by JAKs go to the nucleus to activate gene transcription.