2013研细胞信息转导.ppt

G Proteins Ras Subunit: Trimeric (a, b and g) Monomeric Activation: Dissociation (a and b/g) GEFs Receptor: Direct binding No Signaling: cAMP (PKA) MAP kinase PLC-b: DAG (PKC) IP3 (Ca 2+) G proteins and Ras-Difference Differences among the MAPKs: There are three major MAPK pathways: ERK2, p38 and JNK Dimerization results in autophosphorylation initiating a downstream cascade of events culminating in cellular responses such as cell proliferation or apoptosis. The activated EGF-R dimer complexes with the adapter protein, Grb, coupled to the guanine nucleotide releasing factor, SOS. The Grb-SOS complex can either bind directly to phosphotyrosine sites in the receptor or indirectly through Shc. These protein interactions bring SOS in close proximity to Ras, allowing for Ras activation This subsequently activates the ERK and JNK signaling pathways that, in turn, activate transcription factors, such as c-fos, AP-1, and Elk-1, that promote gene expression and contribute to cell proliferation. HSPG（Heparin Sulfate proteogeycan） 2. PI3K-PKB/AKT pathway Phosphatidyl inositol-3 kinase PI3K can be classifired into four subtypes:PI3Kα、β、γ and S.In RTK mediated signaling pathways, PI3Kα is activated，but in GPCR mediated signaling pathways，PI3Kγ is activated. P1-3K（phosphatidyl Inositol-3Kinase）contains one 85KD regulatory subunit including SH2 domain （P85）and 110KD catalytic subunit（P110）forming dimer and acts as a kinase catalyzing specificly phosphorylation of 3-OH of phosphatidyl Inositol 。 PI3k/Akt (PKB) pathway Insulin Insulin R IRS-1 PI-3 kinase PKB GSK3（糖原合酶激酶） Epo EpoR JAK2 PI-3 kinase PKB TF EGF EGF R Ras PI-3 kinase （磷脂酰肌醇-3激酶） PKB can phosphorylate GSK3 and inactivate it The function of GSK3 is to