Introduction to theIntroduction to the biological biological pathwaypathway

2003.02.072003.02.07POSTECH NLP labPOSTECH NLP lab

발표자발표자 : : 정설경정설경

2003.01.28 NLP lab Introduction to the biological pathway

ContentsContents

IntroductionIntroduction CellCell Biological pathwayBiological pathway

Metabolic pathwayMetabolic pathway Regulatory pathwayRegulatory pathway Signal transduction pathwaySignal transduction pathway GPCR pathwayGPCR pathway Limitation & approachLimitation & approach

2003.01.28 NLP lab Introduction to the biological pathway

• Cell 의 종류•Prokaryote

•Eukaryote

•Plant cell

•Animal cell

Introduction – Cell (1)Introduction – Cell (1)

2003.01.28 NLP lab Introduction to the biological pathway

Introduction – Cell (2)Introduction – Cell (2)

Cell structureCell structure Membrane structureMembrane structure

Plasma membranePlasma membrane Nuclear membraneNuclear membrane

Cell activityCell activity Physiological activityPhysiological activity Chemical activityChemical activity Main component: proteinMain component: protein

2003.01.28 NLP lab Introduction to the biological pathway

인지질의 구조

( phospholipid )

막 구조

( plasma membrane)

2003.01.28 NLP lab Introduction to the biological pathway

2003.01.28 NLP lab Introduction to the biological pathway

Introduction – Cell (2)Introduction – Cell (2)

Cell structureCell structure Membrane structureMembrane structure

Plasma membranePlasma membrane Nuclear membraneNuclear membrane

Cell activityCell activity Physiological activityPhysiological activity Chemical activityChemical activity Main component: Main component: proteinprotein

2003.01.28 NLP lab Introduction to the biological pathway

Protein structure (1)Protein structure (1)

2003.01.28 NLP lab Introduction to the biological pathway

Protein structure (2)Protein structure (2)

2003.01.28 NLP lab Introduction to the biological pathway

Ex> Membrane proteinEx> Membrane protein

2003.01.28 NLP lab Introduction to the biological pathway

Biological pathwayBiological pathway PathwayPathway

사전적사전적 : : 좁은 길좁은 길 , , 오솔길오솔길 , , 진로진로 (course)(course) 생화학생화학 : : 경로경로

Biological pathwayBiological pathway Molecular interaction network in biological Molecular interaction network in biological

processesprocesses Metabolic pathway, Regulatory pathwayMetabolic pathway, Regulatory pathway

Number of Pathway Number of Pathway 9644 pathways (PATHWAY database) 9644 pathways (PATHWAY database) 160 pathways involving 744 reactions and 791 160 pathways involving 744 reactions and 791

substrates (mouse)substrates (mouse)

2003.01.28 NLP lab Introduction to the biological pathway

Metabolic pathwayMetabolic pathway Carbohydrate MetabolismCarbohydrate Metabolism

Glycolysis/GluconeogenesisGlycolysis/Gluconeogenesis TCA cycle (Citrate cycle)TCA cycle (Citrate cycle)

Energy MetabolismEnergy Metabolism ATP synthesisATP synthesis

Lipid MetabolismLipid Metabolism Nucleotide MetabolismNucleotide Metabolism

purine, pyrimidine metabolismpurine, pyrimidine metabolism

Amino Acid MetabolismAmino Acid Metabolism Biodegradation of XenobioticsBiodegradation of Xenobiotics

2003.01.28 NLP lab Introduction to the biological pathway

2003.01.28 NLP lab Introduction to the biological pathway

Regulatory pathwayRegulatory pathway Genetic information processingGenetic information processing

Transcription, Translation, Sorting and Degradation. RTranscription, Translation, Sorting and Degradation. Replication and Repaireplication and Repair

Environmental information processingEnvironmental information processing Membrane transport, Signal transduction, Ligand receMembrane transport, Signal transduction, Ligand rece

ptor interactionptor interaction

Cellular processesCellular processes Cell motility, Cell growth and death, Cell communicatioCell motility, Cell growth and death, Cell communicatio

n, Development, Behaviorn, Development, Behavior

2003.01.28 NLP lab Introduction to the biological pathway

Signal transduction Signal transduction pathwaypathway

Category of signaling proteinCategory of signaling protein Signal moleculeSignal molecule ReceptorReceptor Intracellular signaling proteinIntracellular signaling protein Target proteinTarget protein

4 types of intercellular signaling4 types of intercellular signaling EndocrineEndocrine ParacrineParacrine Neuronal signalingNeuronal signaling Contact-dependent signalingContact-dependent signaling

2003.01.28 NLP lab Introduction to the biological pathway

Modulation by other molecule

Amplification

Divergence to multiple target

2003.01.28 NLP lab Introduction to the biological pathway

2003.01.28 NLP lab Introduction to the biological pathway

Signal transduction Signal transduction pathwaypathway

4 types of intercellular signaling4 types of intercellular signaling EndocrineEndocrine

Broad effect, specific receptorBroad effect, specific receptor hormoneshormones

Paracrine Paracrine Within local tissue, enzyme/extracellular matrixWithin local tissue, enzyme/extracellular matrix

Neuronal signalingNeuronal signaling Synapse of neuron, speedySynapse of neuron, speedy

Contact-dependent signalingContact-dependent signaling Killer T cell (immune system)Killer T cell (immune system)

2003.01.28 NLP lab Introduction to the biological pathway

Signal receptorSignal receptor

Cell surface receptorsCell surface receptors On-Off signalingOn-Off signaling

Ion-channel linkedIon-channel linked G-protein linkedG-protein linked Enzyme linkedEnzyme linked

Intracellular receptorsIntracellular receptors Steroid, Thyroid hormoneSteroid, Thyroid hormone Retinol, Vitamin DRetinol, Vitamin D

2003.01.28 NLP lab Introduction to the biological pathway

2003.01.28 NLP lab Introduction to the biological pathway

G-protein linked G-protein linked receptorsreceptors

Structure of receptorsStructure of receptors N-terminal : extracellular regionN-terminal : extracellular region Seven-span transmembrane domainSeven-span transmembrane domain C-terminal : intracellular signal transduction regionC-terminal : intracellular signal transduction region

Desensitization of receptorsDesensitization of receptors PhospholylationPhospholylation

PKA, PKC or a member of G-protein-linked receptor kinases(GPKA, PKC or a member of G-protein-linked receptor kinases(GRKs) family RKs) family

Receptor inactivationReceptor inactivation Receptor sequestrationReceptor sequestration Receptor down-regulationReceptor down-regulation

2003.01.28 NLP lab Introduction to the biological pathway

G-protein (1)G-protein (1) αα ,,ββ ,,γγ subunit subunit

αα subunit: complex with GDP subunit: complex with GDP

Major familyMajor family

FamilFamilyy

Some Some membemembe

rr

Action Action mediatemediate

ddFunctionsFunctions

I Gs α Activate adenylyl cylclase, Ca2+ channels

II

Gi

α Inhibit adnylyl cyclase

βγ Activates K+ channel

Go

βγActivates K+ channel, inactivate Ca2+

channels

α and βγ Activates phospholipase C-β

Gt α Activates cyclic GMP phosphodiesterase

III Gq α Activates phospholipase C-β

2003.01.28 NLP lab Introduction to the biological pathway

G-protein (2)G-protein (2) Mechanism of G-proteinMechanism of G-protein

ActivationActivation Dissociation of Dissociation of αα-GDP, -GDP, βγβγ complex complex αα-GTP, -GTP, βγβγ complex complex target protein target protein

DeactivationDeactivation G-protein itself: GTPase G-protein itself: GTPase association of association of αα-GDP, -GDP, βγβγ complex complex

Target of activated G-proteinTarget of activated G-protein Direct – ion channel …Direct – ion channel … Indirect – second messengerIndirect – second messenger

Adenylate cylase Adenylate cylase cAMP cAMP Phospholipase C (PLC) Phospholipase C (PLC) diacylglycerol(DAG) & inositol 1,4,5- diacylglycerol(DAG) & inositol 1,4,5-

triphosphate(IPtriphosphate(IP33))

2003.01.28 NLP lab Introduction to the biological pathway

Pathway of indirect Pathway of indirect signalingsignaling

Pathway of cAMPPathway of cAMP cAMP cAMP protein kinas protein kinas

e A e A cell response cell response

Pathway of PLCPathway of PLC DAG DAG protein kinase protein kinase

CC IPIP33 Ca Ca2+2+ ↑ ↑

2003.01.28 NLP lab Introduction to the biological pathway

cAMP pathwaycAMP pathway

2003.01.28 NLP lab Introduction to the biological pathway

PLC pathway (1)PLC pathway (1)

2003.01.28 NLP lab Introduction to the biological pathway

PLC pathway (2)PLC pathway (2) CaCa2+2+ signaling signaling

Regulate 70% of protein kinaseRegulate 70% of protein kinase Regulated by Calcium binding protein, calmodulin(CARegulated by Calcium binding protein, calmodulin(CA

M)M) CaCa2+2+ Ca Ca2+2+-CaM complex -CaM complex CaM-kinase CaM-kinase

2003.01.28 NLP lab Introduction to the biological pathway

exampleexample

Smell receptorSmell receptor

Vision receptorVision receptor

2003.01.28 NLP lab Introduction to the biological pathway

LimitationLimitation

Cannot effectivelyCannot effectively Evaluate them for internal consistencyEvaluate them for internal consistency Evaluate them with consistency for new data : microarrEvaluate them with consistency for new data : microarr

aysays Refine them with respect to new dataRefine them with respect to new data Integrate them to produce system understandingIntegrate them to produce system understanding

They are too large and complexThey are too large and complex The printed word cannot be manipulated effectiveThe printed word cannot be manipulated effective

lyly

2003.01.28 NLP lab Introduction to the biological pathway

Solution: Solution: biological knowledge basesbiological knowledge bases Store biological knowledge and theories in Store biological knowledge and theories in

computers in a declarative formcomputers in a declarative form Amenable to computational analysis and generative Amenable to computational analysis and generative

user interfaces user interfaces

Accepted to store data in computers, but not Accepted to store data in computers, but not knowledgeknowledge Refined, interpreted, consensus viewsRefined, interpreted, consensus views

Establish ongoing efforts to curate (maintain, Establish ongoing efforts to curate (maintain, refine, embellish) these knowledge basesrefine, embellish) these knowledge bases

Such knowledge bases are an integral part of Such knowledge bases are an integral part of the scientific enterprisethe scientific enterprise

2003.01.28 NLP lab Introduction to the biological pathway

Pathway/Genome Pathway/Genome DatabaseDatabase

CELL

pathway

proteins

Genes

operons, promotors, DNA binding site

Chromosomes, plasmid

reactions

compounds