An enzyme-linked receptor—the leptin receptor. The receptor exists as a homodimer (two identical parts), and leptin binds to the extracellular part of the receptor, causing phosphorylation and activation of the intracellular associated janus kinase 2 (JAK2). This causes phosphorylation of signal transducer and activator of transcription (STAT) proteins, which then activates the transcription of target genes and the synthesis of proteins. JAK2 phosphorylation also activates several other enzyme systems that mediate some of the more rapid effects of leptin.
secreted by fat cells and has many physiological effects, but it is especially important in regulating appetite and energy balance, as discussed in Chapter 71. The leptin receptor is a member of a large family of cytokine receptors that do not themselves contain enzymatic activity but signal through associated enzymes. In the case of the leptin receptor, one of the signaling pathways occurs through a tyrosine kinase of the janus kinase (JAK) family, JAK2. The leptin receptor exists as a dimer (i.e., in two parts), and binding of leptin to the extracellular part of the receptor alters its conformation, enabling phosphorylation and activation of the intracellular associated JAK2 molecules. The activated JAK2 molecules then phosphorylate other tyrosine residues within the leptin receptor-JAK2 complex to mediate intracellular signaling. The intracellular signals include phosphorylation of signal transducer and activator of transcription (STAT) proteins, which activates transcription by leptin target genes to initiate protein synthesis. Phosphorylation of JAK2 also leads to activation of other intracellular enzyme pathways such as mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K). Some of the effects of leptin occur rapidly as a result of activation of these intracellular enzymes, whereas other actions occur more slowly and require synthesis of new proteins.
Another example, one widely used in hormonal control of cell function, is for the hormone to bind with a special transmembrane receptor, which then becomes the activated enzyme adenylyl cyclase at the end that protrudes to the interior of the cell. This cyclase catalyzes the formation of cAMP, which has a multitude of effects inside the cell to control cell activity, as discussed in greater detail later. cAMP is called a second messenger because it is not the hormone itself that directly institutes the intracellular changes; instead, the cAMP serves as a second messenger to cause these effects.
For a few peptide hormones, such as atrial natri-uretic peptide (ANP), cyclic guanosine monophosphate (cGMP), which is only slightly different from cAMP, serves in a similar manner as a second messenger.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.