TAMU BIOL 213 - Cell Communication Part 2 (7 pages)

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Cell Communication Part 2

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Cell Communication Part 2


Lecture number:
Lecture Note
Texas A&M University
Biol 213 - Molecular Cell Biol
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BIOL 213 1st Edition Lecture 23 Outline of Last Lecture I Signal transduction a 5 different kinds of signaling II Response to signaling III Intracellular receptors a Ex nitric oxide and steroid hormones IV Cell surface receptors a 3 main kinds i Ion channels G protein coupled receptors enzyme linked receptors b Molecular switches Outline of Current Lecture I Cyclic AMP a Produced by adenylyl cyclase b Primary target is PKA II Inositol triphosphate IP3 diacylglycerol DAG and Ca2 a IP3 and DAG are generated by phospholipase C b IP3 opens Ca2 channels in the ER and Ca2 and DAG activate PKC c Ca2 can bind to other proteins like calmodulin which can then bind to CaMkinase III Enzyme linked receptors a Receptor tyrosine kinases activate signaling proteins b PIP3 c Ras These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute IV Some pathways are activated only if multiple signals are present V Review VI Plant signaling VII Receptor downregulation Current Lecture I Cyclic AMP a Many G protein coupled receptors active adenylyl cyclase b This enzyme produces cyclic AMP from ATP i It connects one oxygen from phosphate to an OH on the sugar ii 2 phosphates are removed from ATP c There is a very low concentration of cyclic AMP inside an unstimulated cell compared to a stimulated cell d It is a second messenger i It diffuses through the cell and interacts with other proteins to initiate a response e Cyclic AMP phosphodiesterase terminates the signal i It converts cyclic AMP to regular 5 AMP ii By breaking the bond between the oxygen and sugar iii Kinases add 2 phosphates to reform ATP iv Caffeine blocks the phosphodiesterase so that the concentration of cyclic AMP stays high f It s primary target is cyclic AMP dependent protein kinase PKA i PKA is activated when cyclic AMP binds to it ii This activated kinase then phosphorylates serines and threonines amino acids on specific proteins g Different target cells have different target proteins i This allows the effect of cyclic AMP to vary in different types of cells ii Ex adrenaline binds to adrenergic receptors 1 Causes the breakdown of glycogen in skeletal muscle cells h Effects can be rapid or slow i Rapid response is when a target protein is altered ii Slow response is when transcription is regulated so that new proteins have to be synthesized II Inositol triphosphate IP3 diacylglycerol DAG and Ca2 a Some G protein coupled receptors activate the membrane bound enzyme phospholipase C b Phosopholipase C with water cleaves an inositol phospholipid called phosphatidylinositol 4 5 bisphosphate PIP2 into two second messangers inositol 1 4 5 triphosphate IP3 and diacylglycerol DAG i IP3 diffuses through the cytosol to bind to and open Ca2 channels in the ER membrane 1 Ca2 diffuses into the cytosol ii DAG stays in the membrane iii DAG and Ca2 both bind to and activate protein kinase C PKC iv PKC then phosphorylates other proteins in the cell to pass on the signal c Ca2 is a second messenger for many pathways i Because the concentration of Ca2 inside the cell is normally really low whenever a high concentration is detected the cell know that there was a signal 1 A Ca2 gradient is created across the ER membrane and the plasma membrane ii Sometimes its effects can be indirect like when it binds to calmodulin 1 This is the most widespread 2 When Ca2 interacts with calmodulin it changes its shape it so that it can interact with several different target proteins 3 An important kind of target protein is Ca2 calmodulin dependent protein kinases CaM kinase a These in turn phosphorylate other proteins III Enzyme linked receptors a These are transmembrane receptor protein where the cytoplasmic domain of the protein either acts as an enzyme or forms a complex with other proteins that will then act as an enzyme b Most enzyme coupled receptors have a cytoplasmic domain that functions as a tyrosine protein kinase i These are called receptor tyrosine kinases RTK c RTKs only have one transmembrane alpha helix so it s hard to translate a conformational change through that i Therefore two RTKs interact and activate each other ii A signal molecule is in the form of a dimer d The phosphorylated tyrosines on the tail of the RTK are docking sites for other proteins i Some of these proteins are phosphorylated and activated ii Some are scaffolding for other proteins e Tyrosine phosphatase inactivates the enzyme complex by removing the phosphate groups from the tyrosines and bound proteins f Some RTKs activate an enzyme called phosphoinositide 3 kinase PI3 kinase that will phosphorylate PIP2 into PIP3 i This is the same PIP2 that is cleaved into IP3 and DAG by phospholipase C ii PIP3 acts as a second messenger to activate other proteins iii PIP3 stays in the membrane iv It activates protein kinase B PKB also known as Akt which is important in the growth and survival of cells g Ras i Ras is a small GTP binding protein that nearly all RTKs activate 1 They are a kind of monomeric GTPase that resembles the alpha region of a G protein 2 It is active when bound to GTP 3 It is inactive when bound to GDP ii A signal molecule activates the RTK iii An adaptor protein binds to the activated tyrosine iv This activates the Ras activating protein Ras GEF v Ras GEF causes the inactive membrane bound Ras to exchange GDP for GTP vi Ras is now active and can pass on the signal vii By initiating a phosphorylation cascade from the plasma membrane to the nucleus viii This includes the MAP kinase signaling module 1 Ras activates MAP kinase kinase kinase 2 Which activates MAP kinase kinase by phosphorylation 3 Which activates MAP kinase by phosphorylation 4 Which phosphorylates target proteins to initiate a response ix Mutations involving the GTPase activity of Ras are found in about 30 of cancers 1 The Ras protein is mutated so that it s never inactivated and continues to transmit signals even without a signal molecule 2 Because Ras is important in signaling cell growth this mutation leads to uncontrollable cell growth 3 Mutant genes that can lead to cancer are called oncogenes IV Some pathways are activated only if multiple signals are present V Review a G protein linked receptors activate G proteins by phosphorylation of GDP to GTP i The and subunits dissociate and activate other proteins ii G proteins can activate adenylyl cyclase 1 Adenylyl cyclase makes cyclic AMP from ATP 2 Cyclic AMP activates

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