Cadherins Cadherin signaling Glycogen synthase kinase

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Описание презентации Cadherins Cadherin signaling Glycogen synthase kinase по слайдам

  Cadherins Cadherins

  Cadherin signaling Cadherin signaling

  Glycogen synthase kinase (GSK-3 beta) GSK-3 Akt/PKB ILK Dsh p 90 RSKPI-3 kinase Wnt Glycogen synthase kinase (GSK-3 beta) GSK-3 Akt/PKB ILK Dsh p 90 RSKPI-3 kinase Wnt ERK Glycogen synthase Cy. Dc-jun -catenin. Integrins

  Cadherins and integrins crosstalk Cadherins and integrins crosstalk

  Tyrosine phosphorylation of β -catenin Tyrosine phosphorylation of β -catenin

  Phosphorylation in cadherin-dependent contacts Phosphorylation in cadherin-dependent contacts

  Cadherin regulation Cadherin regulation

  Wnt signaling  Wnt signaling

  Major morphogens:  - Wnts - Hedgehogs - Notch ligands (Delta-like/Jugged) - BMPs (Bone Major morphogens: — Wnts — Hedgehogs — Notch ligands (Delta-like/Jugged) — BMPs (Bone Morphogenic Proteins) — FGFs — Retinoids

  Wnt palmitoylation Wnt palmitoylation

  Wnt signaling to β -catenin Wnt signaling to β -catenin

  More Wnt signaling to β -catenin More Wnt signaling to β -catenin

  Wnt signaling to Ca and Rho Wnt signaling to Ca and Rho

  Hedgehog signaling  Hedgehog signaling

  Mammalian hedgehogs:  - Sonic hedgehod (SHH) - Indian hedgehog (IHH) - Desert hedgehog Mammalian hedgehogs: — Sonic hedgehod (SHH) — Indian hedgehog (IHH) — Desert hedgehog (DHH)

  Hedgehog modifications Hedgehog modifications

  Hedgehog modifications Hedgehog modifications

  Hedgehog secretion Hedgehog secretion

  Hedgehog signaling Hedgehog signaling

  h. WIF and Shifted h. WIF and Shifted

  Notch signaling  Notch signaling

  Delta-Notch signaling Delta-Notch signaling

  Notch signaling  - Delta-like/Jugged:  Dll 1, 3, 4, Jag 1, 2 — Notch signaling — Delta-like/Jugged: Dll 1, 3, 4, Jag 1, 2 — canonical ligands — Notch — receptor — ADAM (TACE, Kuzbanian) – metalloprotease for S 2 cleavage — γ -secretase complex (presenilin-containing) for S 3 cleavage — N ICD , or NICD, or ICN – transcriptionally active Notch fragment — CSL, CBF 1/RBPJk, Su. H (suppressor of hairless) – transcription factor

  HIF-1 enhances Notch(ICN)-dependent transcription HIF-1 enhances Notch(ICN)-dependent transcription

  TGF R-family receptors TGF R-family receptors

  TGF β -family ligands and receptors TGF β -family ligands and receptors

  TGF β -family ligands TGF β -family ligands

  TGF  signaling and crosstalk with EGFR TGF signaling and crosstalk with EGFR

  TGF  Activins co-receptors TGF Activins co-receptors

  Smad proteins Smad proteins

  TGF β to p 21 Waf 1 and p 15 Ink 4 B TGF β to p 21 Waf 1 and p 15 Ink

  T R-V signaling T R-V signaling

  T R-I, II and V signaling T R-I, II and V signaling

  T GF -induced growth arrest T GF -induced growth arrest

  Signaling to gastrulation Signaling to gastrulation

  STRESS SIGNALING  STRESS SIGNALING

  Reactive oxygen species Reactive oxygen species

  Reactive oxygen species Reactive oxygen species

  ROS  levels 1) Moderate (mostly by NADPH-oxidase to GF,  cytokines, TNF α ROS levels 1) Moderate (mostly by NADPH-oxidase to GF, cytokines, TNF α -like ligands; needed for mitogenic signaling) 2) High (mostly stress-induced; usually pro-apoptotic) 3) The highest – a consequence of mitochondrial disfunction during apoptosis

  Oxidative modifications of proteins Oxidative modifications of proteins

  Signaling targets of ROS  - Tyrosine phosphatases Signaling targets of ROS — Tyrosine phosphatases

  Cell damage targets of ROS  - Tyrosine phosphatases - Proline hydroxylase (PHD) Cell damage targets of ROS — Tyrosine phosphatases — Proline hydroxylase (PHD)

  Signaling targets of ROS  - Tyrosine phosphatases - Proline hydroxylase (PHD) Signaling targets of ROS — Tyrosine phosphatases — Proline hydroxylase (PHD)

  HIF-1 HIF-

  ROS in HIF-1 signaling ROS in HIF-1 signaling

  Signaling targets of ROS  - Tyrosine phosphatases - Proline hydroxylase (PHD) - ASK-1 Signaling targets of ROS — Tyrosine phosphatases — Proline hydroxylase (PHD) — ASK-1 ( via thioredoxin) — JNK ( via GSTp) — PKC — Ras — IKK (to NFk. B) — AP-1, p 53 ( via Ref-1)

  NO  NO

  NO-synthases  - i. NOS (inducible) - e. NOS (endothelial) - n. NOS (neuronal) NO-synthases — i. NOS (inducible) — e. NOS (endothelial) — n. NOS (neuronal)

  Mechanisms of NO action  - S-nitrosylation of proteins - peroxynitryl formation - co-factor Mechanisms of NO action — S-nitrosylation of proteins — peroxynitryl formation — co-factor for soluble guanylate cyclase

  NO and regulation of c. GMP synthesis NO and regulation of c. GMP synthesis

  PKG PKG




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