Chapter 16 Flashcards
Define mitogen
Extracellular signal that leads to cell division
Which types of molecules can directly activate intracellular receptors?
Small and hydrophobic
Define endocrine signaling
Extracellular signals that are broadcast throughout the body via the bloodstream
Define paracrine signaling
Signal molecules diffuse locally through the extracellular fluid and remain near the cell that secreted them
Define autocrine signaling
Cells respond to local mediators that they produced (subcatagory of paracrine)
Define neuronal/synaptic signaling
Nerve cells deliver messages over long distances quickly and specifically
Define contact dependent signaling
Cells make direct physical contact; signal molecules lodged in the plasma membrane of the signaling cell meet receptor proteins embedded in the plasma membrane of the target cell
Describe how hormones activate their receptors. What are their receptors called and where are they located?
bind to nuclear receptor proteins, changing their conformations
these receptors can be in the cytosol or the nucleus
How do hormones and their receptors affect cells?
The activated receptor/hormone complex binds to regulatory portions of genes, activating transcription
Describe hormone response elements
A section of many genes, allows many genes to be regulated by the same protein
Hormones typically regulate ___ sets of genes in different cell types
similar/different
different
What does GPCR stand for?
G-protein coupled receptors
Describe the structure of a GPCR
protein that crosses the membrane seven times by alpha helices
Describe how GPCRs are activated
binding of extracellular signals to the GPCR activates it by causing a conformational change that allows it to bind to a G protein
Describe G-proteins
membrane-bound, trimeric, and activated by GTP
How do GPCRs transmit signals into the cell? (stop at subunit)
binding of a GPCR to a G protein causes it to release its GDP, which causes the G protein to bind GTP (because GTP is more concentrated)
Describe the subunits of the G protein
there is an alpha subunit and a beta/gamma subunit
the alpha is a GTPase, but both can phosphorylate other things
each subunit is attached by lipid anchors to the plasma membrane
What are the two things most commonly activated by GPCRs?
Adenylyl cyclase and phospholipase C
Describe “second messengers”
small, rapidly diffusing molecules that are produced to amplify extracellular signals and leave the membrane to go into the cell
Describe the production of the second messengers IP3 and DAG by GPCR
they are produced from the cleaving of inositol phospholipid by a phosphoipase C that was activated by a GPCR via a G protein called Gq
the IP3 portion leaves and the DAG portion stays
What does IP3 do?
It opens calcium channels in the endoplasmic reticulum
Calcium then binds to calmodulin, enabling it to interact with a wide variety of target proteins, including CaM-kinases
What does DAG do?
It recruits and activates a protein kinase C (PKC) that moved from the cytosol to the plasma membrane
How is cAMP produced and degraded?
an adenylyl cyclase activated by a GPCR produces cAMP from ATP
cyclic AMP phosphodiesterase converts cAMP to AMP
How much cAMP is normally in the cell?
Not much, because the cell wants to be able to respond to small increases
cAMP is broken down to AMP quickly
What are three things that cAMP can do in the cell?
activate PKA’s (cyclic-AMP-dependent protein kinases) that can phosphorylate serines or threonines
lead to phosphorylation of transcription regulators
lead to glycogen breakdown and the inhibition of enzymes that drive glycogan synthesis
What does RTK stand for?
receptor tyrosine kinases
Describe RTKs
largest class of enzyme-coupled receptors, have a cytoplasmic domain that functions as a tyrosine protein kinase, which phosphorylates particular tyrosines on specific intracellular signaling proteins
What are the two things most commonly activated by RTKs?
phospholipase C (the GPCR one) and Ras
How are RTKs activated and inactivated?
binding of a signal molecule causes dimerization and activation of the two subunits which then phosphorylate each other on three sites, allowing other proteins to dock
the tyrosine phosphorylations can be reversed by protein tyrosine phosphatases or activated RTKs can be dragged to the interior of the cell by endocytosis and destroyed by lysosomes
Describe the activation of PIP3 by RTKs
RTKs activate a PI 3-kinase (similarish to phospholipase C), which will activate IP3 by phosphorylation (now be called PIP3)
What does PIP3 do?
PIP3 will act as a docking site for molecules like AKT to be recruited to the membrane and activated
Describe the proteins Bad and BCl2 and their relationship to PIP3
BCl2 inhibits apoptosis, but is inactivated by an un-phosphorylated Bad
PIP3 activates AKT, which will phosphorylate Bad
Describe apoptosis
programmed cell death; a normal part of development and a beneficial response to massive DNA damage
Describe the protein Tor
it is activated by PIP3 and enhances protein synthesis and inhibits protein degradation
Describe protein Ras
a GTPase that is active when bound to GTP and inactive when bound to GDP
lipid anchor to plasma membrane
Describe the activation of Ras by RTKs
the RTK activates and allows docking of an adaptor protein, which activates a Ras-activating (Ras-GEF) that stimulates the release of GDP from Ras
causes Ras to replace GDP with GTP (GTP is more concentrated)
How is Ras inactivated?
a protein called Ras-GAP promotes hydrolysis of GTP
What does Ras do in the cell?
lead to a kinase cascade
MAP kinase kinase kinase activates MAP kinase kinase, which activates MAP kinase (also called MARK, mitogen activated protein kinase)
How is Ras associated with cancer?
It is mutated, such as to be hyperactive
