Calpain Function in the Modulation of Signal Transduction Molecules

• Published in: Biological chemistry Vol. 382; no. 5; pp. 743 - 751
• Main Authors: Sato, K., Kawashima, S.
• Format: Journal Article
• Language: English
• Published: Germany Walter de Gruyter 01.05.2001
• Subjects: Animals; Calcium Signaling - drug effects; Calpain - metabolism; Calpain - pharmacology; Calpain - physiology; Cell Adhesion Molecules - drug effects; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules - physiology; Cytoskeletal Proteins - drug effects; Cytoskeletal Proteins - metabolism; Cytoskeletal Proteins - physiology; Heterotrimeric GTP-Binding Proteins - drug effects; Heterotrimeric GTP-Binding Proteins - metabolism; Heterotrimeric GTP-Binding Proteins - physiology; Humans; Protein Kinases - drug effects; Protein Kinases - metabolism; Protein Kinases - physiology; Signal Transduction - drug effects
• ISSN: 1431-6730; 1437-4315
• DOI: 10.1515/BC.2001.090

Calpains are cytosolic cysteine proteases that are activated by a rise in intracellular Ca[2+], and are believed to function in stimulating Ca[2+] signaling on cell activation, leading the cell to differentiation, proliferation and death. In this review, we focus on the implication of calpains in signal transduction in molecules such as growth factors, T cell receptor, and integrin. Calpains are downstream molecules of hormone receptors, membranetype tyrosine kinases and adhesion molecules, and proteolyze many signalingrelated substrates. The substrates, protein kinase C (PKC), a subunit of Gproteins, and protein tyrosine phosphatases, are cleaved at interdomain site(s) and their activities are sustained or upregulated, while the fragments of focal adhesion kinase and the tyrosine kinase src family lose their activity. In the integrin cascade, calpains are upstream molecules of the Rho GTPase family, Rac1 or RhoA, and allow the lamellipodia formation. The significant activation of calpain suggests that calpain activity is regulated not only by an increase in intracellular Ca[2+], but also by signaling that include the PKC, tyrosine kinase or the adhesion moleculederived cascade. We have summarized these interesting phenomena, and speculate on the function and location of calpain in the signaling cascades.