Life cycle of the budding yeast, S. cerevisiae

Lodish et al, 2000

2n

1n

1n

2n

Haploid yeast cells can be “a” or “a” mating type

Lodish et al, 2000

Mating-type conversionin mother cell

Spore germination

Mating factors induce yeast mating

Lodish et al, 2000

A MAP kinase cascade mediates signalingin the yeast mating pathway

Lodish et al, 2000

Multiple MAP kinase pathways are involved inresponse of yeast cells to stimuli

Lodish et al, 2000

Scaffolds regulate specificity of MAP kinase pathways

Lodish Fig. 20-33

Infection of cells with v-Raf virus leads toactivation of MAPK and MAPKK

MAPKKMAPK

MAPKK

MAPK

MAPKK

MAPK

Control virusNo serum: �Serum: ∆

EC12 virus: �No virus: ∆

22W virus: �

EC12, 22W= mousesarcoma viruses containingactivated v-Raf (N-termtruncation)MAPK activity: assayphosphorylation of MBPMAPKK activity: assayphosphorylation of MBPthrough recombinantinactive MAPK

Dent et al. (1992) Science 257:1401

Phosphorylation activates MAP kinase

Canagarajah et al (1997) Cell 90:859

unphosphorylated phosphorylated Merged and rotated

20.1 Cell-surface receptors belong to fourmajor classes

Figure 20-3c,d

20.4 Ligand binding leads toautophosphorylation of RTKs

Figure 20-21

20.4 An adapter protein and GEF link mostactivated RTKs to Ras

Figure 20-23

SH2 and SH3 domains bind toshort target peptides

Lodish et al, 2000

a) SH2 domain in GRB2 adapter protein binds to a specific phosphotyrosinein an activated RTKb) Sos, a guanine-nucleotide exchange factor, binds to SH3 domains in GRB2

20.4 Structures of Ras·GDP-Sos complex andRas·GTP

Figure 20-27

20.8 From plasma membrane to nucleus

z Many cellular responses induced by water-solublehormones, growth factors, and neurotransmitters result fromtheir effects on gene expression

z Such pathways usually involve activation of protein kinasesthat directly or indirectly phosphorylate specific transcriptionfactors

Khokhlatchev et al (1998). Cell 93:605

Phosphorylation of MAPK leads to nuclear translocation

MAP kinase regulates the activity ofmany transcription factors

Lodish et al, 2000

20.7 Insulin stimulation activates ProteinKinase B and MAP kinase

Figure 20-45

A Ras independent pathway activates Protein Kinase B

20.1 Common signaling pathways areinitiated by different receptors in a class

Figure 20-6