Основные сигнальные пути от рецепторов факторов роста GF GF receptor Ras. GDP TK TK p. Y IP 3 + DAG p. Y Ca PKC 2+ PLC PIP 2 PIP 3 p. Y Ras. GTP Sos Grb 2 p. Y Shc Raf p. S MEK p 110 p 85 p. Y PI-3 K p. Y STAT p. Y p. T ERK PKB STAT p. Y STAT DNA Transcription factors etc.
STAT proteins – signal transducers and activators of transcription
Cytokine receptors
Cytokine receptors, JAKs and STATs Cytokines Signaling molecules Type I Cytokines utilizing γc IL-2, IL-7, IL-9, IL-15 IL-4 Jak 1, Jak 3 Stat 5 Stat 6 Cytokines utilizing βc GM-CSF, IL-3, IL-5 Jak 2 Stat 5 Cytokines utilizing gp 130 IL-6, IL-11, CNTF, LIF, oncostatin M IL-12 Jak 1, Jak 2, Tyk 2 Stat 3 Jak 2, Tyk 2 Stat 4
Cytokine receptors, JAKs and STATs Cytokines Signaling molecules* Cytokines utilizing homodimeric receptor GH Jak 2 Prolactin Jak 2 Erythropoietin, thrombopoietin Jak 2 G-CSF, leptin Jak 2 Type II IFN-α/β IFN-γ IL-10 IL-20 Stat 5 b Stat 5 a Stat 5 Stat 3 Jak 1, Tyk 2 Stat 1, Stat 2 Jak 1, Jak 2 Stat 1 Jak 1, Tyk 2 Stat 3 ? Stat 3
STAT proteins – signal transducers and activators of transcription
STAT proteins
The molecular structure of STAT 1 complex with DNA
The stages of STAT activation from cytokine receptor or from growth factor receptor
STAT proteins
The differentiation of the T-helper cells Th 0 IL-4 STAT 6 IL-12 STAT 4 SOCS-1 Th 2 Th 1
Negative regulation of STATs
PI-3 kinase (phosphoinositide-3 kinase)
Phosphatidylinositol phosphorylation
The classes of the PI-3 kinases
Targets of the PI-3 kinase products
Survival pathways from PKB PI-3 kinase PI-3, 4 -P 2, PI-3, 4, 5 -P 3 m. TORC 2 PDK 1 PKB/Akt Mdm 2 Fox. O GSK 3 Bad Apoptosis NFk. B p 53
PI-3 kinase and cell cycle
Regulation of cell metabolism by PI-3 kinase
Regulation of glycogen synthesis by PI-3 kinase Synip/syntaxin 4 ISPK GSK-3 PP 1 G Glycogen synthase Glycogen
Regulation of translation Erk 1, Er k 2, p 38 P T ranslation activ ated MNK 1 4 G GTP GDP C e. IF 2 P e. IF 2 B GSK 3 4 A 4 E m 7 G 4 G N P AUG. . . A A AAAAA 4 G M 3 4 E-BPs P 40 S 6 S P m. TOR p 70 6 SK 4 E m 7 G AUG. . . A A AAAAA 4 E-BPs T ranslation inhibited MNK 1 4 G C 4 A 4 G N 4 G M
Regulation of PI-3 kinase/Akt by metabolites
Glycogen synthase kinase (GSK-3 beta) PI-3 kinase Integrins Wnt ERK Akt/PKB ILK p 90 RSK Dsh GSK-3 Glycogen synthase c-jun Cy. D -catenin e. IF-2 B
Major PI-3 kinase dependent GEFs for Rac PI-3 K PIP 2(3, 4) PIP 3(3, 4, 5) Vav 1 Vav 2 Rac SWAP-70 P-Rex 1 Dock 180 (indirect)