Mechanisms of signaling by the hematopoietic-specific adaptor proteins, SLP-76 and LAT and their B cell counterpart, BLNK/SLP-65.
Adaptor proteins lack catalytic activity and contain only protein-protein interaction domains. They have been shown to interact with an ever-growing number of signaling proteins and to play essential roles in many signaling pathways. SLP-76 and LAT are cell-type-specific adaptor proteins expressed in T cells, NK cells, platelets, and mast cells. In these cell types, SLP-76 and LAT are required for signaling by immunoreceptor tyrosine-based activation motif(ITAM)-containing receptors, including the T cell receptor (TCR), the pre-TCR, the high-affinity Fc epsilon receptor, and the platelet GPVI collagen receptor. In B cells, an analogous adaptor, BLNK/SLP-65, is required for signaling by the ITAM-containing B cell receptor. This review summarizes recent research on SLP-76, LAT, and BLNK. A major challenge in understanding adaptor protein function has been to sort out the many interactions mediated by adaptor proteins and to define the mechanisms by which adaptors mediate critical signaling events. In the case of LAT, SLP-76, and BLNK, the availability of tractable genetic systems, deficient in expression of each of these adaptor proteins, has facilitated in-depth investigation of their signaling functions and mechanisms of action. The picture that has emerged is one in which multiple adaptor proteins cooperate to bring about the formation of a large signaling complex, localized to specialized lipid microdomains within the cell membrane and known as GEMs. Adaptors not only recruit signaling proteins, but also play an active role in regulating the conformation and activation of many of the proteins recruited to the complex. In particular, recent research has shed light on the mechanisms by which multiple adaptor proteins cooperate to bring about the recruitment and activation of phospholipase C gamma in response to the activation of ITAM-containing receptors.
Yablonski
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Department of Pharmacology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa 31096, Israel.
Weiss
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D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology* / Q000648:ultrastructure; D015870:Gene Expression; D006413:Hematopoietic System / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008957:Models, Genetic; D010750:Phosphoproteins / Q000502:physiology* / Q000648:ultrastructure; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011946:Receptors, Antigen / Q000502:physiology; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011946:Receptors, Antigen; C092947:SLP-76 signal Transducing adaptor proteins