Stat & psoriasis by yousry

Signal Transducer &Activator of Transcription( STAT)-3 :Role in Psoriasis ,[object Object],[object Object]

Signal transducers and activators of transcription ) Stat) Family ,[object Object],[object Object],[object Object]

[object Object],[object Object],[object Object]

STAT 1 STAT 2 STAT 3 STAT 4 STAT 5 STAT 6 SH2 DNA Helix 750 851 DNA SH2 Helix 770 SH2 DNA Helix 748 SH2 DNA Helix 734 SH2 DNA Helix 848 Helix SH2 KGTGYIKTEL 701 ERRKYLKHRL 690 SAAPYLKTKF 705 GDKGYVPSVF AVDGYVKPQI KDGRGYVPAT 693 694 641 Activators IFN-  ,  , IFN  , EGF, PDGF, Insulin, Ang II, VEGF IFN-  ,  Ang II IL-6, LIF, CNTF, ET-1, serotonin, GM-CSF, IL-10, Leptin, EGF, PDGF, Ang II, FGF, VEGF IL-4 and IL- 12 Prolactin, GH, IL-3, Epo, IL- 5, Ang II, Insulin, GM-CSF IL- 4, IL-13, Ang II, PDGF, FGF

[object Object],[object Object],[object Object],[object Object]

[object Object],[object Object]

Ang II NH 2 NUCLEUS c-fos YIPP COOH STAT 1  /  Fyn + SHP-2 + JAK2 SHP-2 JAK2 P STAT 1  /  STAT1  /  STAT1  /  P P STAT1  /  STAT1  /  P P Fyn P P SHP-2 MKP-1 STAT 1  /  P P Fyn P P JAK2-STAT1 activation

NK-22 cell-secreted cytokines stimulate epithelial cells to proliferate, release IL-10 and activate STAT1 and STAT3. M Cella et al. Nature 000, 1-4 (2008)

CYTOKINES, CYTOKINE RECEPTORS, ACTIVATED SIGNALING MOLECULES AND MAJOR BIOLOGICAL FUNCTIONS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

STAT3 Activation ,[object Object],[object Object],[object Object],[object Object]

Mechanism of Stat3 signaling ,[object Object]

Class IIB(3)(b) latent cytoplasmic factors These families not present in fungi or plants, hinting at an important evolutionary divergence leading to animals.

STATs - a signal responsive TF family ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

The JAK-STAT signalling pathway ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Canonical JAK–STAT pathway ,[object Object],[object Object],[object Object],[object Object]

IFN-response: two variants ,[object Object],[object Object],[object Object],[object Object],[object Object]

STAT-family members ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

STAT-STAT interaction occurs through reciprocal phospho-Tyr - SH2 interactions ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Y P Y P Y + Y

Dimerization via SH2-Tyr P Tyr P from the left monomer SH2 from the right monomer

STATs - structure and function ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],GAS= TTN 5-6 AA ISRE= AGTTTN 3 TTTCC

STAT-STRUCTURE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Promoter recognition and selectivity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Transactivation Domain(TAD) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Other functional domains ,[object Object]

Psoriasis ,[object Object],[object Object]

Psoriasis Clinical Presentation

Psoriasis as an immune disorder

Immunomodulator(Alefacet) effect on Psorasis Area Score Index(PASI)

ANTI –Tumor Necrosis Factor (TNF) in Psoriasis

Stat3 links activated keratinocytes and immunocytes required for development of psoriasis ,[object Object],[object Object],[object Object],[object Object],[object Object]

Do Other Therapies Work Within This Framework? ,[object Object],[object Object]

Studies on Stat 3 in Psoriasis

The JAK-family of tyrosine kinases ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

The role of the kinases in the signalling pathway INF  -signalling INF  -signalling

The cytokine-receptor superfamily ,[object Object],[object Object],[object Object],[object Object]

Specificity in response ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Several signalling pathways linked ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Cross Talks ,[object Object],[object Object],[object Object],[object Object],P P P P P P P P JAK SH2 Cytokine receptor Y Y Y Y P P P Receptor tyrosinee kinase MAPK

Variations in mechanisms of STAT activation

SMAD-family - a logic resembling the STAT-family ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

TGF  effectors ,[object Object],[object Object]

Classification ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

SMAD-signalling pathway Effector SMADs (R-SMADs) C o-SMADs Repressor SMADs

Three groups of SMADs ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Final steps - target gene activation ,[object Object],[object Object],[object Object]

The Smad-factors activate their target genes in combination with other TFs

Stat & psoriasis by yousry

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Stat & psoriasis by yousry