Gly-Arg-Gly-Asp-Ser, Synthetic integrin antagonist

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The integrin alpha 2b + beta 3 also known as GPIIb/IIIa is an important protein complex involved in platelet aggregation. This integrin functions as a receptor for fibrinogen and aids in the clotting process. It is a heterodimer consisting of the alpha IIb subunit and the beta 3 subunit together weighing approximately 160 kDa and 90 kDa respectively. These subunits are primarily expressed on the surface of platelets. Additionally integrin alpha 5 acts as the fibronectin receptor and is commonly found on fibroblasts endothelial cells and other cell types.

Biological function summary

Integrin alpha 2b + beta 3 plays a critical role in hemostasis. As part of a large and functionally diverse family of integrins it facilitates platelet adhesion and aggregation by binding to fibrinogen and initiating cross-linking. This complex is essential for normal clot formation following vascular injury. Integrin alpha 5 forming dimers with beta 1 contributes to cell adhesion and migration by interacting with fibronectin. Through these interactions integrins modulate various cell processes such as survival proliferation and differentiation.

Pathways

Both integrin alpha 2b + beta 3 and alpha 5 participate in the integrin-mediated signaling pathway. This pathway involves the transition from a low-affinity to a high-affinity binding state known as inside-out signaling which modulates subsequent outside-in signaling leading to actin cytoskeleton rearrangement. The PI3K/AKT pathway is one example where these integrins interact with proteins like focal adhesion kinase (FAK) to influence cellular responses. The interaction contributes to platelet activation and cell motility playing essential roles in normal physiological and pathological processes.

Integrin alpha 2b + beta 3 is strongly related to thrombotic diseases. Abnormalities such as Glanzmann thrombasthenia result from defects in this integrin leading to bleeding disorders due to impaired platelet function. It is also a target for antithrombotic drugs known as integrin antagonists which inhibit its interaction with fibrinogen. On the other hand integrin alpha 5 is involved in cancer metastasis where it facilitates tumor cell migration and invasion. Its overexpression links to increased cancer cell dissemination interacting with proteins such as matrix metalloproteinases to support tumor progression.