12-7-09_MicrotubuleMotors_lectureA

12-7-09_MicrotubuleMotors_lectureA - “Science is the...

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Unformatted text preview: “Science is the belief in the ignorance of the experts” – Albert Einstein There is a theory which states that if ever anybody discovers – Douglas Adams Announcements • Quiz 9 (last one) is due this Wednesday at noon. • Review questions will be given out today or tomorrow. You’ve activated the receptor, now what? Different signaling proteins a) Adaptor proteins : link signaling proteins with SH2 domain b) Docking proteins: can add tyrosine phosphorylation sites c) Transcription factors: Activated factor goes directly to nucleus to regulate genes (STAT protein shown in example, involved in immune function) d) Other signaling enzymes, such as PLC-gamma, PI3K, phosphatase MAP kinase pathway 1) Glucose regulation, cell proliferation and differentiation 2) Dysregulation, especially via Ras, is a common route to cancer 3) Receptor activation induces intracellular phosphorylation 4) An adaptor protein such as Grb2 can bind to activated receptor and to Sos (a GEF) 5) Sos activates Ras-GDP to Ras-GTP MAP kinase pathway • Sos activates Ras-GDP to Ras- GTP • Enter the kinase cascade, Raf, MEK, ERK • MAPKKK is a MAP kinase kinase kinase, because it phophorylates sequentially two steps away from MAPK • MEK is a dual-specificity kinase and can work on tyrosine or serine-threonine • Activated MAPK into the nucleus to phosphorylate transcription factors • Transcription factors regulate genes • MAPK turned off by MAPK phosphatase (MKP-1) upregulated by transcription factor Inhibitory Dual PKA action activates glycogen breakdown and inhibits glycogen synthesis pathways • Phosphorylation by PKA activates phosphorylase kinase (1) and inhibits glycogen synthase by activating a kinase to phosphorylate glycogen synthase (2) 1 2 CREB/CRE are critical for coupling receptor activation to long-term changes in the cell • cAMP response element binding protein (CREB) is a common target for intracellular pathways (Aplysia sensitization, glucose regulation, etc) • PKA phosphorylates CREB and CREB dimerizes • CREB binds to the cAMP response element (CRE), which is a nuclear DNA sequence. CREB binding will upregulate transcription of multiple genes that are coupled to CRE, usually related to a unified function (e.g....
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12-7-09_MicrotubuleMotors_lectureA - “Science is the...

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