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Biochemistry, 4th Edition P109

Biochemistry, 4th Edition P109. Continuing Garrett and Grisham's innovative conceptual and organizing framework, "Essential Questions," BIOCHEMISTRY guides students through course concepts in a way that reveals the beauty and usefulness of biochemistry in the everyday world. Streamlined for increased clarity and readability, this edition also includes new photos and illustrations that show the subject matter consistently throughout the text. New end-of-chapter problems, MCAT practice questions, and the unparalleled text/media integration with the power of CengageNOW round out this exceptional package, giving you the tools you need to both master course concepts and develop critical problem-solving skills you can draw upon. | 32.7 How Do Neurotransmission Pathways Control the Function of Sensory Systems 1043 the cell s response to inflammation caused by infection. This is an example of transactivation of a GPCR by a RTK. The reverse can happen as well. GPCRs can transactivate RTKs by a variety of mechanisms. For example in certain neurons in the hypothalamus stimulation of ft1-adrenergic receptors triggers a G-protein-mediated pathway that activates a matrix metalloproteinase. Metalloproteinase action releases heparin-binding EGF-like growth factor HB-EGF in the extracellular matrix. Binding of HB-EGF to the EGF receptor initiates a classic RTK-activated signaling pathway Figure 32.46b . Signals from Multiple Pathways Can Be Integrated A cell can be exposed simultaneously to multiple potentially contradictory signals in the form of soluble hormones and ligands anchored to adjacent cells or the extracellular matrix. Cells must have mechanisms for sorting these various signals into a defined response. The Rsk1 protein serine threonine kinases exhibit such behavior integrating several signals to achieve full activation. Rsk1 has two protein kinase domains Figure 32.47 of which the N-terminal domain phosphorylates downstream targets. This N-terminal kinase domain is controlled by multiple inputs including from the C-terminal domain. The Erk MAPK binds to a docking site at the C-termi-nus of Rsk1 phosphorylating sites in the linker region between the two kinase domains and in the C-terminal domain all of which are essential for activation. Full activation however also requires phosphorylation of the N-terminal kinase domain by the PIP3-stimulated PDK1 protein kinase. Rsk1 activation thus requires inputs from both the Erk MAPK pathway and the PIP3 pathway Figure 32.47 . PI3K Multiple signaling inputs t Ras FIGURE 32.47 Integration of signaling pathways. Activation of a ribosomal serine threonine kinase known as Rsk1 requires phosphorylation by two protein kinases a phosphoinositide-dependent