rtk bio

Rtk structure and importnace

Rtk is a single pass recptor with intrinsic kinase activity!

It is formed by a transmembrane alpha helix and has 2 domain one extracellular and one cytosolic tyrosin kinase domain

Describe the two domains of rtk

1. The extracellular domain is the one for the LIGAND and where ex. Gf bind

2. Is the TYROSIN CYTOLOSIC DOMAIN. That is the enzymatic part where tyrosin is phophorylated KINASE DOMAIN NEED contact for activation that is why DIMERIZATION IS THE FIRST STEP

What are the 3 steps from binding the ligand to having activation of the docking sites?

1. Ligand induces dimerization as kinase domains need contant to be activated so the ligand make the 2 recpetos come toghter AS IN EGF ( IF THE LIGAND IS ALREADY A DIMER it simply brings the two recpetors toghter

2. Autophosophorilation ( THE RECEPTORS PHOPHORYLATE ONE ONTHOR ON TYROSIN RECPETORS

3. CREATION OF DOCKING SITES FOR SH2 AND PTB

What are the effecte of autophophorilation

After dimerization, autophophorilation allowa the activaion of the kinase domain ad the creation of docking sites for both phophpylated tyrosin domains ( sh2 and ptb)

Sh2 is for JUST PHOP. TYROSIN

Ptb is for PHOPHOYORISIN CONTAINING SEQUENCES

ENZYME COUPLED RECPETORS have what chracteristics compered to SECOND MESSANGERS OR gpcr

1 no g protei

2. Have intrinisic kinase activity or is directly associated with an enzyme DIRECTLY!

Which are the 4 main rtk activated signaling pathways

1. Small GTPase

2. Map

3. Pi3/akt

4. Plcgamma2/ dag/ ca2+ signaling

Small gtpase are activated by rtk which are the main 4

Rho: cytoskelton dynamics

Ras: for survival and proliferation

Ran: fro cyto to nuclear transport

Rab: for vescile traficking

How does RAS gtpase drives cancer

Growh factor activates rtk, dimerization, autophoph. Docking for SH2 that recuits RAS EF. THAT ACTIVATES RAS

Ras in cancer: for mutation ras is always active as mutation inhibit gtp hyrolisis and it is not turned off.

Describe the patwhay from ras to second response genes

1. Ras activates ERK extracellular signal regulated kinase

2. Erk enter nucleus and there is a proliferation of trasncprition factors

   1. Rapid transcription of INTERMEDIATE EARLY GENES

   2. These genes are activated by SERUM RESPONSE GENES

   3. SRE activates second response gene

What is activated by RAS THAT allows a rapid intermediate early gene transcription

Erk that goes into the nucleus

While erk enters the nucleus, where are RAS located

Always in the pm attached via a FARNESYL tail

Define map kinase and how this group avoid unwanted cross walk and mantain specificity

1. Map kinase ee SERINE/ TYROSINE KINASE present in all eukaryotic cell!+

2. Are actiated by rtk

3. EACH MAP IS A CASCADE OF 3 KINASES

4. Mantain specificity thorugh SCAFFOLD THAT put them in one module to avoid unwanted crosswalk

Rtk activate also a pathway that is also simultaneusly activated by beta gamma complecy og GCPR which is it?

Pi3k that allows pip2 to pip3 recuiting PH ( domain for plasma membrane)

How does ATK promotoes survivival?

Atk promotoes survival by phophorilating BAD BAD is inhibited!! ( hen bad is active it pronotes apoptosis)

How does ATK promotes cell growth?

Atk allows the activation of RHEB rheb activates MTOR THAT ALLOWS MORE RIBOSOME PRODUCTION AND PROTEIN SYNTHETISI WHITOUTH MTOR THERE IS NO CELL GROWTH

Mtor is activated by atk that is activated by rtks what is the function of mtor?

Atk allows the activation of RHEB rheb activates MTOR THAT ALLOWS MORE RIBOSOME PRODUCTION AND PROTEIN SYNTHETISI WHITOUTH MTOR THERE IS NO CELL GROWTH

PLC IS NORMALLLY ACTIVATED THROUGH BETA GAMMA COMPLEX OF GPCR how does RTK ACTIVATES PLC AND WHAT IS THE RESULT

Plc gamma is activated by RTK once the docking sites of sh2 are active!

Then plc gives PI2 that hydolysises into Dag and IP3

What is the main difference between RTK and NRTK

Non rtks are non covently associated with surface receptors

This recpetors DO NOT HAVE INTRINSIC KINASE ACTIVITy so they must associate with separate kinase

Describe the. Structure of NTRK

As rtks they have: a extracellular ligand domain

A transmembrane alpha helix

But the cytosolic domain has the NON RECEPTOR TYROSIN KINASE

Describe the 4 steps to activate NRTK

1. Ligand binds, DIMERIZATION

2. 2. CROSS PHOPHORILATION

3. HE ACTIVATED KINASE ( NON LORO) phophorilate the receptos

4. Phophorylated tyrosin become the docking sites

5. Recuitmenet

What is an essential patway rom NRTKs for CYTOKINES RECPETORS?

JAK AND STAT

Jak: janus kinase, with tyrosine kinase receptors fro cytokines

STAT; signal trasducer and activator of transcription of sh2 domain

So are SIGNALING MOLECULES AN TRASNCRIPTION FACTORS AT THE SAME TIME

Where is stat inactive? How is it activated? Where does it go once it activates<?

Stat is inactive in the cytosol, as the cytokines bind the receptors on JAK and tyrosin is phophorylated s

Stat binds it dimerizes after phophorylateion and TRANSLOCATE TO THE NUCLEUS WHERE IT ACTIVATES THE TRANSCRIPTION OF TARGET GENES