信号转导及异常.ppt

(2) PI3-kinase/Protein kinase B pathway PKB(or Akt) containing a PH domain --Binds to PI(3,4,5)P3 --Activated by a phosphatidylinositol-dependent protein kinase PDK1 --Phosphorylates and inactivates BAD, a pro-apoptosis factor, promotes cell survival Cross-talk between signaling pathways activated by GPCRs and RTKs Cytokines --receptors --Jak-STAT signal pathway 2. Tyrosine-kinase-associated receptors STATs also contain SH2 domain and dock onto specific activated receptor TK, thus being activated independent of Jaks Ligands: interferons, cytokines, etc JAK family: JAK1-3, Tyk 2 (Just Another Kinase/Janus Kinase) (cytoplasmic tyrosine kinases) STAT family: STAT1-7 (Signal Transducer and Activator of Transcription Jaks phosphorylate and activate STATs --STATs then move to the nucleus and stimulate transcription 3. Receptor serine/threonine kinasesTGF-b superfamily--receptor serine/threonine kinases--Smads Signal Pathway Transforming growth factor-b superfamily: TGF-bs, activins, bond morphogenetic proteins (BMPs), etc TGF-β Receptor Superfamily: Protein serine/threonine kinase; Single pass transmembrane receptor; Type I and II The ligand first binds to and activates type II homodimer, which recruits, phosphorylates, and activates a type I receptor dimer, forming a tetrameric receptor complex Smads 4. Receptor guanylyl cyclases Receptor guanylyl cyclases: single pass transmembrane proteins Generates cGMP in response to stimuli, cGMP binds to and activates a cGMP-dependent serine/threonine protein kinase (PKG) Atrial natriuretic peptides (ANPs) as signal molecules: regulate salt and water balance and dilate blood vessles Nuclear Receptors Steroid Receptors Retinoid Receptors Orphan Receptors Nuclear receptors are ligand-activated gene regulatory proteins Some small hydrophobic signal molecules, such as steroids, thyroids, retinoids, and vitamin D, can diffuse directly across the plasma membrane to bind