Overview: Biological Signaling
 
Cellular signaling is the process by which cells perceive stimuli from information molecules through the cell membrane or intracellular receptors, which are converted by intracellular signaling systems, thereby affecting the biological functions of the cell. The environment in which higher organisms live changes all the time, and the functional unity of the organism requires a well-developed mechanism of intercellular recognition, mutual response, and interaction, which can influence the performance and regulation of proliferation, differentiation, metabolism, and death in the whole life process.
 

First, Second and Third Messengers

Hormones, neurotransmitters, cytokines, growth factors, etc. are synthesized and released by cells and transported by diffusion or body fluids and are the "first messengers" of the body's information transmission. "The earliest signaling substance produced in the cell after the first messenger interacts with the receptor is called the "second messenger". Currently recognized "second messengers" include cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), inositol triphosphate (IP3), etc., whose functions are to initiate and assist in the amplification of intracellular signals step by step. Third messengers: Substances responsible for signaling inside and outside the nucleus, also known as DNA-binding proteins. Second messengers activate a specific class of nuclear proteins along with specific protein kinases. Phosphorylated nuclear proteins recognize and bind to specific regulatory sequences on target genes, causing changes in gene transcription. These nuclear proteins are synthesized in the cytoplasm and then enter the nucleus, where they play the role of messengers and are the third messengers for transmitting life information.
 

Characterization of Signaling Molecules

• Specificity: it can only bind to specific receptors; 
• High efficiency: a few molecules can have obvious biological effects, such as the concentration of various hormones in the blood is extremely low, generally only a few ug or even a few ng per 100mL of blood, but the physiological regulation of the human body is very significant;
• Can be inactivated: when completing a signal response, the signaling molecules will be inactivated through modification, hydrolysis, or binding and be eliminated in time to ensure the integrity of the information transfer and cell fatigue-free.

cAMP

cAMP is the "second messenger" of life information transmission, and is an important regulator of life, which exists in micro quantities in various cells of plants and animals and microorganisms. It is an important substance involved in the regulation of material metabolism and biological functions within the cell. When a variety of hormones in the body act on the cell, it can prompt the cell to produce this substance, which in turn regulates the physiological activities of the cell and material metabolism.

Position of cAMP in the KEGG Pathway

The cAMP signaling pathway is a type of cyclic nucleotide signaling pathway. Like most signaling types of pathways, the cAMP pathway begins with extracellular signals binding to the appropriate receptor and then regulates downstream intracellular signaling by modulating the concentration of the intracellular second messenger cAMP.
 
Among the KEGG core 35 pathways, the cAMP pathway is entirely on the right side of this cluster, i.e., it belongs to the cluster of signaling-related pathways. The cAMP pathway exists in direct connection with a total of 4 of these 35 pathways and does not appear to be as popular as, for example, the MAPK pathway.
   
The 25 pathways directly related to the cAMP pathway are categorized by class A, and 15 of them belong to Organismal Systems. Most of the pathways under the Organismal Systems category are Endocrine systems, which shows that the cAMP pathway is related to a large number of endocrine-related pathways. In addition, the cAMP pathway is associated with several tumor-related signaling pathways, including the PI3K-AKT pathway.
 

Regulation of Physiological Activities by cAMP

CAMP and cell proliferation and differentiation
CAMP and hormone synthesis and secretion
CAMP and membrane protein activity
CAMP and neural activity
CAMP and gene expression
CAMP and olfactory activation
 
cAMP signaling is a pathway with a wide range of intracellular roles and is involved in almost all aspects of biology. the upstream part of the cAMP pathway is relatively simple and accordingly can be targeted for therapeutic purposes. Normally, intracellular cAMP levels are regulated by a balance between the activities of two enzymes, AC and PDE, in response to hormones and neurotransmitters.
 

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