Figure 720

Role of multiple transcription factors and primary response genes in mediating protein synthesis in response to a first messenger binding to a plasma-membrane receptor.

kinase in the signal transduction pathway triggered by first-messenger binding to that very receptor; thus, this receptor inactivation constitutes a negative feedback.

This concludes our description of the basic principles of signal transduction pathways. It is essential to recognize that the pathways do not exist in isolation but may be active simultaneously in a single cell, exhibiting complex interactions. This is possible because

PART TWO Biological Control Systems

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

PART TWO Biological Control Systems

TABLE 7-7 Reference Table of Important Second Messengers

Substance

Source

Effects

Calcium

Enters cell through plasmamembrane ion channels or is released from endoplasmic reticulum

Activates calmodulin and other calcium-binding proteins; calcium-calmodulin activates calmodulin-dependent protein kinases

Cyclic AMP (cAMP)

A G protein activates plasmamembrane adenylyl cyclase, which catalyzes formation of cAMP from ATP

Activates cAMP-dependent protein kinase (protein kinase A)

Cyclic GMP (cGMP)

Generated from guanosine triphosphate in a reaction catalyzed by a plasma-membrane receptor with guanylyl cyclase activity

Activates cGMP-dependent protein kinase (protein kinase G)

Diacylglycerol (DAG)

A G protein activates plasmamembrane phospholipase C, which catalyzes generation of DAG and IP3 from plasma membrane phosphatidylinositol bisphosphate (PIP2)

Activates protein kinase C

Inositol trisphosphate (IP3)

See DAG above

Releases calcium from endoplasmic reticulum

a single first messenger may trigger more than one pathway and, much more importantly, because a cell may be influenced simultaneously by many different first messengers—often dozens. Moreover, a great deal of cross-talk can occur at one or more levels among the various signal transduction pathways. For example, active molecules generated in the cAMP pathway can alter the ability of receptors that, themselves, function as protein kinases to activate transcription factors.

Why should signal transduction pathways be so diverse and complex? The only way to achieve controlled distinct effects by a cell in the face of the barrage of multiple first messengers, each often having more than one ultimate effect, is to have diverse pathways with branch points at which one pathway can be enhanced and another reduced.

The biochemistry and physiology of plasmamembrane signal transduction pathways are among the most rapidly expanding fields in biology, and most of this information, beyond the basic principles we have presented, exceeds the scope of this book. For example, the protein kinases we have identified are those that are closest in the various sequences to the original receptor activation; in fact, as noted earlier there are often cascades of protein kinases in the remaining portions of the pathways. Moreover, there are a host of molecules other than protein kinases that play "helper" roles.

Finally, for reference purposes, Table 7-7 summarizes the biochemistry of the second messengers described in this chapter.

SECTION B SUMMARY

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Essentials of Human Physiology

Essentials of Human Physiology

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.

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