Signaling mechanisms utilized by antigen receptors and integrins: common intermediates, different outcomes?
Antigen receptors and integrins are structurally and functionally distinct, but both play key roles in regulating immune cell activation and function. Understanding the molecular basis of the signaling pathways utilized by antigen receptors and integrins is fundamental to identifying the mechanisms underlying immune system function and dysfunction (e.g. autoimmune disease) and identifying potential targets for modifying the immune response with therapy. Recently, several key regulators of antigen receptor signaling have also been revealed to be important molecular intermediates in integrin-triggered signaling pathways. These include the protein tyrosine kinase Syk, the guanine nucleotide exchange factor Vav, and the adaptor protein SLP-76. While antigen-receptor signaling is generally associated with leukocyte activation and differentiation, integrins are most commonly thought of as adhesive receptors. This raises the interesting question of how common molecular intermediates may regulate diverse cellular processes such as activation versus adhesion and migration, and provides a framework for defining potentially unique mechanisms utilized by cells of the immune system to regulate integrin-dependent cell function.
Luckashenak
Nancy
N
Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo NY 14263, USA.
Clements
James Lindsey
JL
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008213:Lymphocyte Activation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase