CXCL12-activated CXCR4 signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by the binding of the C-X-C chemokine CXCL12 to a C-X-C chemokine type 4 receptor (CXCR4) on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:nhn]

CXCL12, also known as stromal cell-derived factor-1 (SDF-1), is a chemokine that plays a crucial role in various biological processes, including cell migration, immune cell trafficking, and angiogenesis. CXCL12 exerts its effects through binding to its cognate receptor, CXCR4, a G protein-coupled receptor (GPCR) expressed on various cell types. The CXCL12-activated CXCR4 signaling pathway is a complex cascade of molecular events that ultimately lead to cellular responses.

**Step 1: Ligand Binding and Receptor Activation:**

The process begins with CXCL12 binding to the extracellular domain of CXCR4. This interaction triggers a conformational change in the receptor, leading to its activation.

**Step 2: G Protein Coupling and Activation:**

Activated CXCR4 interacts with a heterotrimeric G protein, specifically the Gαi subunit. This interaction causes the dissociation of the Gαi subunit from the βγ dimer, leading to its activation.

**Step 3: Downstream Signaling Cascades:**

The activated Gαi subunit inhibits adenylyl cyclase, reducing the production of cyclic adenosine monophosphate (cAMP). Simultaneously, the activated βγ dimer activates phospholipase C (PLC), leading to the production of inositol triphosphate (IP3) and diacylglycerol (DAG).

**Step 4: Calcium Signaling and Cellular Responses:**

IP3 triggers the release of calcium ions (Ca2+) from intracellular stores, leading to increased intracellular calcium levels. This calcium influx activates various downstream signaling pathways, including protein kinase C (PKC) activation. DAG, in turn, also activates PKC.

**Step 5: MAPK Activation and Gene Regulation:**

The CXCL12-CXCR4 signaling pathway also activates mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK) and p38 kinase. Activated MAPKs phosphorylate various downstream substrates, including transcription factors, leading to alterations in gene expression.

**Step 6: Cellular Responses:**

The CXCL12-activated CXCR4 signaling pathway orchestrates a wide range of cellular responses, including:

* **Cell migration and chemotaxis:** CXCL12 acts as a chemoattractant, guiding cells towards its source. This process is crucial for immune cell trafficking, wound healing, and development.
* **Cell survival and proliferation:** The pathway can promote cell survival and proliferation, playing a role in tissue regeneration and tumor growth.
* **Angiogenesis:** The signaling pathway promotes the formation of new blood vessels, contributing to vascular development and repair.
* **Immune modulation:** CXCL12 plays a role in regulating immune cell activation, differentiation, and migration, influencing the immune response to infections and inflammation.

**Conclusion:**

The CXCL12-activated CXCR4 signaling pathway is a crucial regulator of various biological processes, orchestrating cellular responses that are essential for maintaining tissue homeostasis, immune defense, and development. Its complex interplay of molecular events highlights the intricate mechanisms by which cells communicate and respond to their environment.'
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Proteins (2)

Compounds (13)