White - Cell Communication 2 Flashcards
What does PKA stand for and what does it do?
Protein Kinase A; it is the downstream target of cAMP that acts on target proteins
When GPCR attaches to G-alpha-q or G-alpha-o, what is the effector in this case?
Phospholipase C instead of adenylyl cyclase
What does phospholipase C do?
Cleaves PIP2 which produces IP3 and DAG 2nd messengers
What is the function of IP3?
Releases Ca2+ from the ER by binding to an IP3-gated Ca2+ channel and triggers opening
What is the function of DAG?
Binds to protein kinase C along with Ca2+, causing a conformational change and activating PKC
What is the function of PKC?
Phosphorylates a variety of membrane and cytoplasmic substrates
Calmodulin
Protein that calcium binds to and can bind and activate other proteins to activate their functions
CaM Kinase II
Calmodulin-dependent kinase; can phosphorylate transcription factors so they can bind to DNA for transcription
Receptor Tyrosine Kinases (RTKs)
Play important role in signal transduction; enzyme linked receptors; enzymatic domain is in the cytoplasmic tail of the integral membrane protein; binds growth factor through extracellular domain
Growth Factors
Proteins released by cells to promote growth of other cells; cause cells to proliferate and grow in cell culture
Examples: Epidermal Growth Factor (EGF), Platelet Derived Growth Factor (PDGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF), Insulin-like Growth Factor 1 (IGF-1)
Components of RTKs
Extracellular domain, transmembrane domain, cytoplasmic domain (transmits signal through tyrosine kinase domain); adds phosphate to tyrosine on proteins
RTK Activation
- Ligand binding to this receptor causes a conformational change that induces dimerization of two receptor monomers
- Autophosphorylation occurs
- This causes the receptor to act as a scaffold to recruit other proteins to the plasma membrane
- Receptor does NOT bind to G protein but to proteins with a domain called the SH2 domain, which binds to phosphotyrosine, such as Grb2
- Grb 2 also has SH3 domain that binds to prolines in SOS (Son of Sevenless), which then binds to Ras (small monomeric G protein - small GTPase)
- Ras binds Raf which initiates MAP Kinase Cascade
What is SOS?
A GEF that exchanges GDP for GTP on Ras
Ras
First discovered human oncogene; plays crucial role in cell division and a frequent mutation in cancer
What is MAP Kinase and what does it do?
Mitogen Activated Protein Kinase; plays a role in cell proliferation