《病理学与病理生理学总论》6 信号转导异常与疾病.pptVIP

Activated MEK then phosphorylates another protein kinase called MAPK causing its activation. This series of phosphylating activations is called a kinase cascade. It results in amplification of the signal Mechanism of Tyrosine Kinase Receptors Among the final targets of the kinase cascade are transcriptions factors (fos and jun showed here). Phosphorylation of these proteins causes them to become active and bind to the DNA, causing changes in gene transcription Mechanism of Tyrosine Kinase Receptors Signal Transduction Through Receptor Tyrosine Kinases EGF signaling pathway Each cytokine/hematopoietic receptor is a composite of structurally distinct protein domains. Members of this receptor family contain one, two, or even three polypeptides. The transmembrane domain consists of a single alpha helix of about 20 amino acids. Ligand binding occurs at a domain near the transmembrane domain Cytokine Receptors The cytosolic domain of a cytokine receptor does not possess intrinsic catalytic activity. Rather, the ligand-bound receptor recruits and activates the cytosolic tyrosine kinase JAK. JAK substrates include JAK itself, the receptor, IRS molecules, and the transcriptional activator STAT. Phosphorylated JAK also interacts with other signal transduction proteins through SH2 domains Type I and type II receptors for TGF(beta) in a cell prior to binding of the growth factor. Binding of growth factor results in clustering of type I and type II receptors, and phosphorylation of type I receptors by type II receptors. The activated type I receptors then phosphorylate particular receptor-mediated Smads. These Smads then bind to other Smads (co-Smads), and together they enter the nucleus. Receptor serine/threonine kinase mediated pathway TGF-? signaling pathway Intracellular (nuclear) receptor mediated pathway Basic Structure of nuclear receptor Hormone-bindind domain DNA-binding domain Transcription-activating domain The signal pathway by steroid hormones n