The seven transmembrane ?-helix structure of a G protein-coupled receptor.

Along with cytokine receptors and growth factor receptors, for the new MCAT you need to be familiar with the pathways involved in signal transduction with G protein-coupled receptors.

Both single-celled organisms and cells within tissues can respond to changes within their extracellular environment, changes which trigger a biochemical series of events within the cell. The general mechanism involves the binding of extracellular molecules (signaling ligands) to specific receptors. The receptors then communicate the event of binding to the cell's interior through a signal transduction mechanism initiated by changes in the receptor, such as conformational changes or receptor dimerization.

Many different specific receptors have been identified that operate on the surface of human cells within various tissues. Signaling receptors fall within four general classes. The first class are the enzyme linked receptors which include the cytokine receptor family and growth factor receptor family. G protein-coupled receptors constitute the second class. For future doctors it is relevant to note that G protein-coupled receptors are the most important targets in modern pharmacology. The third group are receptors found intracellularly, which, upon ligand binding, proceed to alter gene transcription as transcription factors. The fourth class are ligand gated ion channels.

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Learning Goals

Proficiency 

Understand how to distinguish endocrine, paracrine, autocrine, contact, and intracrine signaling.

Be able to distinguish the major structural classes of receptors in terms of their general mechanisms of signal transduction.

Be prepared to describe general motifs occuring in signal transduction including protein kinase cascades, GTPase activity, and activation of phospholipases.

Be able to describe the role of ubiquitinylation and proteosome degradation in regulating signaling pathways.

Know the purpose of SH2 domains.

Be prepared to unpack their acronyms and describe the activity of JAKs and STATs in signaling from cytokine receptors.

Understand why mutant forms of Ras are often found in human cancers.

Be able to describe the chemical reactions that bring about IP3 and DAG production and signaling consequences involving calmodulin and protein kinase C.

Be able to narrate the structural changes that occur upon activation of heterotrimeric G proteins and subsequent activation of adenylate cyclase and protein kinase A.

Be prepared to describe the basic structural plan and mechanism of action of a nuclear receptor.

Become comfortable in discussions involving the structure, function, and regulation of ligand-gated ion channels.

Suggested Assignments

Conceptual Vocabulary for Signal Transduction













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