Lecture 03 – General aspects of molecular signaling pathw - PowerPoint Presentation

Slide1

Lecture 03 – General aspects of molecular signaling pathways and cellular signaling

BIOL 5190/6190 Cellular & Molecular

Singal

Transduction

Prepared by Bob Locy

Last modified -13FSlide2

G Protein Coupled Receptor Pathways

G Protein Coupled Receptors

Seven membrane-spanning domain receptors

Heterotrimeric G-proteins

Activate different second-messenger systems

cyclic AMP based

IP3 based

Second messengers work to modulate effectors that

mediate cellular responsesSlide3

General principle of the GPCR

signaling

system.

Vilardaga J et al. J Cell

Sci

2010;123:4215-4220

©2010 by The Company of Biologists LtdSlide4

GPCRs

Vilardaga J et al. J Cell

Sci

2010;123:4215-4220Slide5

Modulation of G-protein signaling by receptor heterodimers.

Vilardaga J et al. J Cell

Sci

2010;123:4215-4220

©2010 by The Company of Biologists LtdSlide6

Module 1: Figure stimuli for cyclic AMP signalling

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Slide7

Module 1: Figure stimuli for InsP3/DAG signalling

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Slide8

Tyrosine and histidine kinases

Histidine

kinase

receptors are among most widely known types of receptors.

Also known as

phosphorelay

receptorsSlide9

Figure 1 Two-component histidine

kinases

and more complex

phosphorelay

systems

Biochemical Society Transactions (2013) 41, 1023-1028 - Paul V. Attwood

www.biochemsoctrans.orgSlide10

Tyrosine and Histidine Kinase Receptors

Approximately

20 different

Receptor

Tyrosine Kinase classes have been identified

. [

KEGG, 2010] RTK class I (EGF receptor family) (ErbB family) RTK class X (LTK receptor family) RTK class II (Insulin receptor family) RTK class XI (TIE receptor family)

RTK class III (PDGF receptor family)

RTK

class XII (ROR receptor family)

RTK class IV (FGF receptor family)

RTK

class XIII (DDR receptor family)

RTK class V (VEGF receptors family)

RTK

class XIV (RET receptor family)

RTK class VI (HGF receptor family)

RTK

class XV (KLG receptor family)

RTK class VII (

Trk

receptor family) RTK class XVI (RYK receptor family)

RTK class VIII (Eph receptor family)

RTK

class

XVII (

MuSK

receptor

family)

RTK class IX (AXL receptor family)Slide11

Tyrosine and Histidine Kinase Receptors

Most

RTKs

are single subunit receptors but some exist as

multimeric

complexes, e.g., the insulin receptor that forms disulfide-linked

dimers

in the absence of hormoneLigand binding to the extracellular domain often induces formation of receptor dimers

.

Each monomer has a

single

hydrophobic transmembrane-spanning domain composed of 25-38 amino acids, an extracellular N-terminal region, and an intracellular C-terminal region.

The extracellular N-terminal region exhibits a variety of conserved elements including immunoglobulin (

Ig

)-like or epidermal growth factor (EGF)-like domains,

fibronectin

type III repeats, or

cysteine

-rich regions that are characteristic for each subfamily of

RTKs

; these domains contain primarily a

ligand

-binding site, which binds extracellular

ligands

, e.g., a particular growth factor or hormone.

The intracellular C-terminal region displays the highest level of conservation and comprises catalytic domains responsible for the

kinase

activity of these receptors, which catalyses receptor

autophosphorylation

and tyrosine

phosphorylation

of RTK substrates.Slide12

Module 1: Figure stimuli for enzyme-linked receptors

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Slide13

Module 1: Figure tyrosine kinase-linked receptors

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Slide14

Module 1: Figure PDGFR activation

Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012