cell communication 2
DESCRIPTION
luyTRANSCRIPT
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INTRACELLULARSIGNALING
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Jalur penghantaran signal intraselular
- Molekul pembawa signal (ligand)/first messenger
- Reseptor- Second messenger- Intracellular signal- Protein target- Respon
Figure 6-3: Signal pathways
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Receptor
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Reseptor- Tempat pengikatan first messenger
secara spesifik- Umumnya terdapat pada membran sel,
beberapa reseptor ada yang tersimpan dalam sitosol atau inti (contoh: reseptor untuk hormon pertumbuhan)
- Terdapat 3 jenis tipe (seperti kuliah sebelumnya)1. Ion channel-linked receptor2. G protein-coupled receptor3. Enzyme-linked receptor
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Tipe receptor yang terdapat pada permukaan membran
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Lokasi receptorSitosol atau nukleus
- Untuk ligand yang bersifat Lipophilic dan mampu menembus membran sel
- Bersifat mengaktifkan gene
- Respon lambat
Membran sel
- Ligand yang bersifat Lipophobic dan tidak mampu menembus membran sel
- Terletak dipermukaan membran sel
- Respon cepat
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Lokasi receptor(steroid receptor)
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Lokasi receptor hormon steroid
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Ligand
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Ligand- Dapat berikatan secara spesifik pada reseptor- Molekul yang bersifat endogen atau eksogen Endogen : Hormon pertumbuhan
InsulinInterleukin
Eksogen : Molekul obat- Terdapat 3 tipe :
- Agonis (selektif / non selektif)-- aktivasi- Antagonis (selektif / non selektif)--
menghambat aktivasi- Partial agonis / antagonis
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Second messenger
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Second messenger- Molekul pembawa signal yang terdapat didalam
sel sebagai penerus informasi / signal
- Konsentasinya dapat meningkat atau menurun tergantung aktivasi ekstraselular
- Berupa :
1. Ion (Ca2+)
2. Molekul protein (ATP, IP3, protein G, PKA, PKC)
3. Enzim (kinase, posfatase, posforilase)
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Calcium as an intracellular messenger
Second messenger padaion channel-linked receptor
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Second messenger padaG protein-coupled receptor
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Example: Tyrosine kinase
Second messenger padaenzyme-linked receptor
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Cell signaling
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Cell signaling- Bagaimana sel menerima, mengolah dan
merespon signal dari lingkungannya.- Dalam organisme multiselular terdapat berbagai
molekul signal yang dilepaskan atau diekspresikan pada permukaan sel
- Molekul akan berintegrasi dan berkoordinasi membentuk fungsi yang utuh dalam kehidupan organism.
- Prokariotik dan uniseluler eukariotik bersifat independent dan autonomous
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Jenis hantaran signal
1. Signal transduction1. Signal amplification2. Relay signal
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1. Signal transduction
- Merubah energi signal
- Protein kinase
- Melalui aktivasi second messenger
1. Phosporilasi
2. Ikatan dengan Ca
- Menghasilkan respon
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2. Signal amplification
- Signal yang kecil menghasilkan respon yang besar
- Amplification enzyme
- Cascade (rangkaian proses)
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3. Relay signals- Signals yang diterima oleh reseptor pada
permukaan membran (G-protein-linked atau enzyme-linked receptor)direlay ke dalam sel
----> untuk molekul yang berukuan kecil dan besar
- Menghasilkan rangkaian intracellular signaling dengan mengubah protein target
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- Mediator intraseluler yang berukuran kecil disebut second messengers (first messenger selalu berada diluar sel)e.g. Ca2+ dan cyclic AMP, yang water-soluble dan
dapat berdifusi kedalam sitosol
- Mediator intraseluler yang besar disebut protein intracellular signaling---> meneruskan signal dengan mengaktifkan
protein target selanjtnya atau menghasilkan mediator lain didalam sel
Relay signals
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Relay signals
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Relay signals
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Relay proteins: pass the message to the next signaling component
Adaptor proteins: link one signaling protein to another without themselves participating in the signaling event
Amplifier proteins: usually either enzymes or ion channels that enhance the signal they receive
Transducer proteins: convert the signal to a different form e.g. adenyl cyclase
Bifurcation proteins: spread the signal from one signaling pathway to another
Peran protein pada signaling pathway
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Integrator proteins: receive signals from 2 or more pathways and integrate thembefore relaying a signal onwards
Latent gene regulatory proteins: activated at the cell surface by activated receptors & migrate to the nucleus to stimulate gene expression
Modulator proteins: modify the activity of intracellular signaling proteins & regulate the strength of signaling along the pathway
Anchoring proteins: maintain specific signaling proteins at a specific location by tethering them to a membrane
Peran protein pada signaling pathway
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Scaffold proteins: adaptor &/or anchoring proteins that bind multiple signaling proteins together in afunctional complex
Peran protein pada signaling pathway
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Mekanisme aktivasi protein signal
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Protein intracellular signaling sebagai molecular switch
- Beberapa protein intracellular signaling bersifat sebagaimolecular switches
----> Pada saat menerima signal, mereka merubah dari keadaan inactive menjadi active
- Terdapat 2 kelompok molecular switches
1.Phosphorylation switches
2.GTP-binding protein switches
----> keberadaan gugus posfat menunjukkan apakan protein tersebut dalam keadaan aktif atau inaktif.
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Switch is turned on by a protein kinase, which adds a phosphate, and turned off by a protein phosphatase, which removes the phosphate group
Switch is turned on by exchange of GDP for GTP, and turned off by GTP hydrolysis (ie GTPase activity)
Protein intracellular signaling sebagai molecular switch
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Respon cell signaling
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1. Signalling pathway
3. Genetic network
2. Metabolic pathway
STIMULUS
Respon dari sel signaling
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Contoh : (1) hormon steroid
- Hormon steroid akan berdifusi menembus membran sel dan berikatan dengan reseptornya yang terdapat dalam sitoplasma atau nukleus.
- Termasuk: 1. Hormon seks (estrogen, progesterone, testosterone) 2. Corticosteroids (glucocorticoids + mineralcorticoids) 3. Hormon thyroid , vitamin D3 dan asam retinoat
- Berpengaruh terhadap pembentukan faktor transkripsi yang dapat berfungsi sebagai :1. Aktivator2. Inhibitor
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(2)Respons penurunan kadar glukosa darah oleh insulin
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Respon dari sel signal