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Paper: Illustrate the multi-channel, multi-link, multi-level and networked regulation of cell signal transmission and its significance with examples.
What are the main transmission pathways of cell signal transduction?

1 mediated signal transduction pathway. G protein can bind to guanine nucleotide reversibly. Heterotrimers composed of X and γ subunits play an intermediary role between membrane receptors and effectors. Small G protein only has the function of G protein subunit and participates in intracellular signal transduction. After the information molecule binds to the receptor, it activates different G proteins in the following ways: (1) Adenosine cyclase pathway increases or inhibits the activity of adenosine cyclase (AC) and regulates the intracellular cAMP concentration by activating different subtypes of G protein. CAMP can activate protein kinase A(PKA), cause phosphorylation of various target proteins and regulate cell function. (2) Phospholipase pathway activates phospholipase C(PLC) on cell membrane, and catalyzes the hydrolysis of plasma membrane phosphatidylinositol diphosphate (PIP2) to produce inositol triphosphate (IP3) and diglyceride (DG). IP3 promotes the release of Ca2+ stored in sarcoplasmic reticulum or endoplasmic reticulum. Ca2+ can be used as a second messenger to start a variety of cellular reactions. Ca2+ binds to calmodulin and activates Ca2+/ calmodulin-dependent protein kinases or phosphatases, resulting in various biological effects. DG and Ca2+ can coordinate the activation of protein kinase C(PKC).

2. Receptor tyrosine protein kinase (RTPK) signal transduction pathway The receptor tyrosine protein kinase superfamily is characterized by its own tyrosine protein kinase (TPK) activity, and its ligand is mainly growth factor. RTPK pathway is closely related to cell proliferation and hypertrophy and tumorigenesis. After the ligand binds to the extracellular domain of the receptor, the receptor has (TPK) activity after dimerization and catalyzes the autophosphorylation of tyrosine residues in the intracellular domain. The downstream signal transduction of RTPK is activated by serine/threonine protein kinase cascade: (1) mitogen-activated protein kinase (MAPK), (2) protein kinase C(PKC) and (3) phosphatidylinositol 3 kinase (PI3K), thus triggering the corresponding biological effects.

3. Non-receptor tyrosine protein kinase pathway The similarity of this pathway is that the receptor itself has no TPK activity, and the ligands are mainly hormones and cytokines. Its regulation mechanism is very different. If the ligand binds to the receptor to dimerize the receptor, PLC-β can be activated by G protein or PLC-γ can be activated by binding to phosphorylated TPK in cytoplasm, thus triggering the cell signal transduction cascade.

4. Signal transduction pathway of receptor guanylate cyclase Nitric oxide (NO) and carbon monoxide (CO) can activate guanylate cyclase (GC), increase cGMP production, cGMP activates protein kinase G(PKG), and phosphorylates target protein to play a biological role.

5. Nuclear Receptor Signal Transduction Pathway Intracellular receptors are distributed in cytoplasm or nucleus, which are essentially transcription factors regulated by ligands, all of which initiate signal transduction and affect gene transcription in the nucleus, and are collectively called nuclear receptors. Nuclear receptors are divided into steroid hormone receptor family and thyroxine receptor family according to their structure and function. Steroid hormone receptors (except estrogen receptors) are located in cytoplasm, and exist in combination with heat shock protein (HSP), so they are inactive. The binding of ligand to receptor separates HSP from receptor, exposing DNA binding region. The activated receptors dimerize and migrate into the nucleus, and combine with hormone response elements (HRE) on DNA or interact with other transcription factors to enhance or inhibit gene transcription. Thyroxine receptor is located in the nucleus and does not bind to HSP. After the ligand binds to the receptor, the receptor is activated and the gene transcription is regulated by HRE.

In short, cellular information transmission pathways include ligand receptors and transduction molecules. Ligands mainly include hormones, cytokines and growth factors. Receptors include membrane receptors and intracellular receptors. Transduction molecules include small molecular transducers and macromolecular transduction proteins and protein kinases. Membrane receptors include 7 transmembrane α -helix receptors and 1 transmembrane α -helix receptors. The former includes PKA pathway, PKC pathway, Ca+ and calmodulin-dependent protein kinase pathway and PKG pathway, and the second messenger molecule such as cAMPDGIP3CacGMP participates in the information transmission of these pathways. The latter membrane receptors mediate TPK-ras-MAPK pathway and JAKSTAT pathway. The ligands of intracellular receptors include steroid hormones, vitamin D3, thyroxine and retinoic acid. Intracellular receptors are inducible transcription factors, which combine with ligands to produce transcription factor activity and promote transcription. The signals of extracellular information molecules are transmitted to cells or nuclei through cell information channels, which have many biological effects, such as the opening or closing of ion channels, the change of ion concentration, the change of enzyme activity and substance metabolism, the change of gene expression and the influence on cell growth, development, differentiation and appreciation.