8. Regulatory domains

15. ligands inactive tyr kinase monomer … cross-phosphorylation of tyrosines Receptor Tyrosine Kinase Activation ATP ADP Phosphorylated tyrosines on activated signaling proteins  cell response active tyr kinase dimer P- P- P- -P -P -P X X X

16. ligands inactive tyr kinase monomer cross-phosphorylation of tyrosines MAP ( mitogen-activated protein ) kinase activation: ATP ADP active tyr kinase dimer GDP GTP Ras inactive active MAP kinase-kinase-kinase active nucleus P- P- P- P- P- -P -P -P X X X adaptor protein Ras-activatingprotein MAP kinase-kinase MAP kinase translocation to nucleus…

17. P | nucleus P- P- MAP kinase Transcription factors Other nuclear proteins DNA binding Changes in protein activity changes in gene activity Cell proliferation, differentiation

19. Tyr-P Grb2 SH3 domains Proline-rich regions (-PXXP-) Sos Ras (inactive) Pi Ras (active) Raf MEK MAP kinase P P P Nucleus MAP kinase P P fos jun P P Increase gene expression SH2 domain GDP GTP DNA