Week 8 Chapters 9 and 10
Week 8 Chapters 9 and 10 Bio 1510
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This 9 page Class Notes was uploaded by Nausheen Zaman on Sunday October 25, 2015. The Class Notes belongs to Bio 1510 at Wayne State University taught by Dr. Nataliya Turchyn in Summer 2015. Since its upload, it has received 629 views. For similar materials see (LS) Bas Life Mch in Biology at Wayne State University.
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Date Created: 10/25/15
Chapter 9 Cont o Kinase Cascades Making a Signal Bigger o Kinase Cascades Series of protein kinases that phosphorylate each other in succession 0 Protein kinases makes signal bigger I Signal amplification makes a signal bigger o Signals include growth factors shortlived ligands I Growth factors stimulate cell division and growth 0 Activators are proteins I They activate kinases gt other kinases chain reaction 0 MAP mitogenactivated protein kinases amplify signal I Stimulates cell division I A few signal molecules can elicit a large cell response 0 Each step of the cascade the signal becomes bigger and bigger more response proteins are reached gt leads to several different cell responses 0 Occurs during normal cell division Signal amplification l Hampton l Activator Gellular responses o RASMAP Kinase Pathway o RAS protein that stimulates cell division I Links RTKs gt MAP kinase cascade o RAS active when GTP guanosine triphosphate bound to it inactive when GDP guanosine diphosphate is bound to it o Dimerization activates kinases gt kinases autophosphorylate each other I Phosphate groups from kinases then go to activate RAS protein gt activated MKKK MAP Kinasequot3 gt activates MKK via phosphorylation O gt activates MK via phosphorylation gt activates response proteins MK phosphorylates different response proteins gt initiates cellular response Uncontrolled RAS productionfunction uncontrollable cell division 0 GProtein Coupled Receptors O O O O Activate an effector protein usually an enzyme Largest family of membranesurface cell receptors I Consist of seven alphahelices I Called GPCR because it is linked to Gprotein 0 Three subunits alpha beta gamma I Gprotein can be active or inactive 0 Active When GTP bound to alpha subunit 0 Inactive When GDP bound to alpha subunit When ligand hormoneneurotransmitter binds to GPCP gt GPCR undergoes conformational change gt binds to Gprotein gt alpha subunit exchanges GDP for GTP Gprotein becomes active gt active gprotein splitsdissociates gt GTPbound alpha subunit betagamma complex gt each of them binds to effector protein enzyme making it activeinactive gt cellular response Alpha subunit hydrolyses GTP gt GDP Pi GDP reassociated with betagamma complex making Gprotein inactive c When Effector Protein Adenylyl Cyclase is Activated O O O Begins with GTP binding to adenylyl cyclase and activating it I Adenylyl cyclase catalyzes conversion of ATP gt cAMP Adenylyl cyclase enzyme produces cyclic AMP cAMP I cAMP binds toactivates enzyme protein kinase A PKA PKA phosphorylatesactivates specific proteins 0 cAMP Effects 0 O O O O Adenylyl cyclase shared between heart skeletal muscle and fat cells A single ligand adrenaline can lead to different effects in different cells I Different response proteins are phosphorylated into different cells Adrenaline epinephrine hormone produced by adrenal glands Greceptor goes through conformational change and activates Gprotein PKA regulates different response proteins by phosphorylation I Response proteins differ between different cells This knowledge is used by pharmaceutical companies who are attempting to come up with a new drug to target something ie insulin shots I The earlier you target in signal pathway gt more side effects you get I Later you target in signal pathway gt more specific your drug effect would be CAMP Effects Adrenaline 6 proteinscoupled receptor gt G protein PKA9 CAMP9 Adenylyl cyclose Shared between Response Response Response heart protein 1 protein 2 protein 3 m itlzland A fat cells Increase In lBr39eokdowln Breakdown heart rate of glycogen of fats to Differs to glucose fatty ocuds In between in SKElB l l fair cells different muscles cells c When Effector Protein Phospholipase C is Activated O Phospholipase C enzyme becomes active when GTP from alpha subunit binds to it Phospholipase C catalyzes the cleavage phosphatidylinositol 45 biP PIP2 gt inositol 145 triP IP3 and diacylglycerol DAG I IP and DAG are 2nol messengers DAG stays attached to membrane P3 travels to smooth ER to open Ca2 channel releases Ca2 to flow from lumen to cytoplasm I Ca2 ions flow down concentration gradient with passive transport facilitated diffusion o Facilitated by the presence of Ca ion channel in membrane protein I much higher concentration of Ca ions in smooth ER than in cytoplasm Ca2 binds to calmodulin or PKC Ca2 binding proteins leading to different cellular responses I PKC protein kinase C Ca ions CMP DAP P3 o Phospholipase C Effects 0 O 0 Liver has the receptor where vassopresin binds gt causes liver cells to break down glycogen to glucose I Insulin converts glucose gt glycogen I Vassopresin breaks down glycogen gt glucose Pancreas smooth muscle has the receptor for acetylcholine neurotransmitter I Causes smooth muscles to contract Thrombine protease found in blood plasma Table Mai Some Responses Mediated by Phospholipsss Astitiom Molecule Target Tissue Major Response Vssopressin a protein hormonsji ll39isrsr EIFEGII breakdown Asstylsholine secretes faigrestive Ei Zquot acetylrcholilne smooth muscle contraction Thrombi n a pro39tsollytic blood platelets aggregation llQ39Q39E EFIFtL HJEl FUELIEIillhl Different Ligands Same Effect 0 0 Different receptors can produce the same 2 messengers Hormones glucagon and epinephrine can both stimulate liver cells to breakdown glycogen to glucose I both act by same signal transduction pathway Glucagon produced in alpha cells of pancreas Glu 6P becomes a free glucose that is distributed around the body gt Level of glucose increased in the blood Liver cells have receptors for epinephrine glucagon insulin and vassopresin I Epinephrine vassopresin and glucagon increase blood glucose levels by breaking down glycogen to glucose when fastingexercising I Insulin decrease blood glucose levels by converting excess of glucose to glycogen A single cell has many different receptors that activate the samedifferent signaling pathways by activating MAPK cascadeproducing different 2 messengers When twomore signaling pathways cross each other known as crosstalk at Epinephrine 1 FUR Adenwyl I 39 I 39gl gwuase 39 7 LIL Gilycog en la Gllrucose Ephosphate moter 10 How Cells Divide Allows new cells to form from preexisting cells asexual reproduction reproduction without sex a without Mitosis type of asexual reproduction during which a single parent cell divides only once to produce two genetically identical daughter cellsoffspring 0 allows to grow out damaged cells Somatic cells soma body are all cells in the body except for egg and sperm Somatic liver skeletal muscle blood cells produced by mitosis Eggsperm gametesgerm cells produced by meiosis DNA 0 DNA Packaging 0 Chromosomes structure made of material called chromatin that is made up of DNAproteins 0 Each somatic cell body cells has 46 chromosomes 23 pairs 23 chromosomes from mom 23 from dad Structure of a Chromosome 0 Paternal C1O inherited from dad Maternal C1O inherited from mom 0 Homologous chromosomes have the same length genes and loci positions of genes on the chromosomes do not necessarily have the same versions of the genes 0 Centromeres constricted regions of chromosomes every chromosome has one centromere o Kinetochore protein complex which microtubules that separate chromosomes bind 1 kinetochore per chromosome 0 Telomere each eukaryotic chromosome has 2 telomeres which are repetitve noncoding DNA sequences which do not encode any proteins but protect the chromosome ends from degeneration from nucleases and fusion with other chromosomes Paternal Maternal W chromosome 10 chromosome 10 Kinetachar39e I 39 Telamems o The Human Karyotype Karyotype analysis a picture of all your chromosomes in one somatic cell When chromosomes tightly packed condensed can be easily distinguished from each other when the cell begins to divide 0 When chromosomes loosely packed decondensed cannot be distinguished from each other I Cell being tested must begin to divide o Chromos 144 Cpairs 122 are autosomes nonsex chromosomes DOES NOT DETERMINE THE GENDER OF THE ORGANISM o Chromo 23 Cpairs 4546 are sex chromosomes determines sex of organism I Male XY chromosomes not homologous I Female XX chromosomes homologous Eggsperm gametesgerm cells have 23 chromosomes each in humans Egg X Sperm has X or Y mfki jl l I a39ili idm l393 39iLI1i II F Em hEII39TIEEQUE EEI Mai ili39 l39ik u m Keryotype belongsto mole We can determine Gender oi chromosomes The length and size oi chromosomes Genetic disorders associated with the lengths oi chromosomes 0 Heterochromatin vs Euchromatin o In dividing cells all chromatin is tightly packedcondensed o Nondividing cells can be either tightly packed or loosely packed o Heterochromatin tightly packed chromatin with tightly packed DNA which cannot be expressed can t be used to make proteins found centromeres and telomeres of chromosomes both in dividingnondividing cells 0 Euchromatin loosely packed chromatin whose DNA is loosely packed which can be expressed and used to make proteins nondividing cells only 0 When your Cells are Not Dividing o Histones DNA packaging proteins include H1 H2A HZB H3 H4 I H2A H4 core histones consists of 8 core histones 2 of each core histone I H1 linker histone o Nucleosome complex of 8 core histones DNA wrapped around them basic unit of DNA packaging in eukaryotes o No histones in prokaryotes but found only in eukaryotes When Your Cells are Not Dividing 39 llistone core Linker histone Nltlcllear Nucmear quot ENNEUOHE Nucleosome para as 39 complex uchromatin quot39sulator heterochromatin lt 0 Cell Cycle Mature nerve and skeletal muscle cells do not divide Blood skin cells divide every day liver cells divide once a year Centrosome microtubule organizing center a place where microtubules come out from forming mitotic spindle separation of chromosomes during cell division 2 centriolescentrosome centrioles found in animals only Interphase preparation for M Mitotic phase longest phase of cell cycle I M phase mitosis nucleus division prophase prometophase metaphase anaphase and telophasePPMAT cytokenisis cytoplasm divides 0 At end of M phase two daughter cells are created with exact genetic copies of chromosomes Cell Cycle Gap 2 cell ends L H f39S gg wwmmquot Pause in G1 centrosome l Metaphase phase where duplication nerveskeletal continues to grow muscle cells biggerand gets stay ready for division permanently 39 whileliver cells stay for 6 i 1lnlerphase months then Ell G I f i gobacktoG1 Synthes39s S39 212iisneslsM Phase phase Cell duplicates chromosomes and DNA centrosome Gap 1 cell grows duplication but doesn39t divide begins 0 Duplicating the DNA in the 8 Phase 0 Cohesion protein complex that holds two identical sister chromatids together each sister chromatid has its own DNA molecule 0 During S phase number of chromosomes does not change but the appearance of chromosomes changes Nonsister chromatids homologous chromatids2 sister chromatids Liver cells 46 Chromos 46 DNA gt after 8 phase gt 46 chromosomes 92 chromatids92 DNA molecules 0 After DNA is Duplicated o lnterphase G2 I Cell has 2 centrosomes 0 Each centrosome contains 2 centrioles I Each chromosome consists of 2 identical sister chromatids held together with cohesin I Nuclear envelope is intact 0 G1 1 centrosome 2 centrioles G2 2 centrosomes 4 centriole