Scaffold Protein Summary
| Scaffold Proteins | Pathway | Potential Functions | Description |
|---|---|---|---|
| KSR | MAPK | Assembly and localization of the RAS-ERK pathway | One of the best studied signaling pathways in biology is the RAS-ERK pathway in which the RAS G-protein activates the MAPKKK RAF, which activates the MAPKK MAPK/ERK kinase 1 (MEK1), which then activates the MAPK ERK. Several scaffold proteins have been identified to be involved in this pathway and other similar MAPK pathways. One such scaffold protein is KSR, which is the most probable equivalent of the well-studied yeast MAPK scaffold protein Ste5. It is a positive regulator of the pathway and binds many proteins in the pathway, including all three kinases in the cascade. KSR has been shown to be localized to the plasma membrane during cell activation, thereby playing a role in assembling the components of the ERK pathway and in localizing activated ERK to the plasma membrane. |
| MEKK1 | MAPK | Assembly and localization of the death receptor signalosome | Other scaffold proteins include B-cell lymphoma 10 (BCL-10) and MEK kinase 1 (MEKK1), which have roles in the JUN N-terminal kinase (JNK) pathway. |
| BCL-10 | MAPK | Assembly and specificity of JNK | |
| AHNAK-1 | Calcium signaling | Assembly and localization of calcium channels | Calcium signaling is essential for the proper function of immune cells. Recent studies have shown that the scaffold protein, AHNAK1, is important for efficient calcium signaling and NFAT activation in T cells through its ability to properly localize calcium channels at the plasma membrane . In non-immune cells, AHNAK1 has also been shown to bind calcium channels with phospholipase Cγ (PLC-γ) and PKC. Calcium binding proteins often quench much of the entering calcium, so linking these calcium effectors may be especially important when signals are induced by a weak calcium influx. |
| HOMER | Calcium signaling | Inhibition of NFAT activation | Another example of a scaffold protein that modulates calcium signaling is proteins of the HOMER family. The HOMER proteins have been shown to compete with calcineurin to bind to the N terminus of NFAT in activated T cells. Through this competition, the HOMER proteins are able to reduce NFAT activation, which also reduces the production of the IL-2 cytokine. In contrast, HOMER proteins have also been shown to positively regulate calcium signaling in neurons by linking the glutamate receptor with triphosphate receptors in the endoplasmic reticulum. |
| Pellino | Innate Immune Signaling | Assembly of the TLR signalosome | Evidence exists that Pellino proteins function as scaffold proteins in the important innate immune signaling pathway, the Toll-like receptor (TLR) pathway. Much Pellino function is speculation; however, Pellino proteins can associate with IRAK1, TRAF6, and TAK1 following IL-1R activation, indicating that they may assemble and localize components of the TLR pathway near its receptor. |
| NLRP | Innate Immune Signaling | Assembly of the inflammasome | The NLR family is a highly conserved and large family of receptors involved in innate immunity. The NLRP (NLR family, pyrine domain-containing) family of receptors function as scaffolds by assembling the inflammasome, a complex that leads to the secretion of pro-inflammatory cytokines such as IL-18 and IL-1β. |
| DLG1 | T-cell receptor signaling | Assembly and localization of TCR signaling molecules, activation of p38 | DLG1 is highly conserved in immune cells and is important for T-cell activation in the periphery. It is recruited to the immunological synapse and links the ζ-chain of the T-cell receptor (TCR) to CBL, WASP, p38, LCK, VAV1, and ZAP70. This data suggests that DLG1 plays a role in linking TCR signaling machinery with cytoskeleton regulators and also suggests a role in alternatively activating the p38 pathway. However, it is unclear to whether DLG1 positively or negatively regulates T-cell activation. |
| Spinophilin | Dendritic cell signaling | Assembly of DC immunological-synapse proteins | Spinophilin is involved in dendritic cell function specifically in the formation of immunological synapses. Spinophilin is recruited to the synapse following dendritic cell contact with a T cell. This recruitment seems to be important because without spinophilin, dendritic cells cannot activate T cells in vitro or in vivo. How spinophilin facilitates antigen presentation in this case is still unknown though it is possible that spinophilin regulates the duration of cell contact in the synapse or regulates the recycling of co-stimulatory molecules in the cell like MHC molecules. |
| Plant FLU regulatory protein | Coordination of negative feedback during protochlorophyllide biosynthesis. | Assembly and localization of the pathway that turns of synthesis of highly toxic protochlorophyllide, a precursor of chlorophyll. | Synthesis of protochlorophyllide must be strictly regulated as its conversion into chlorophyll requires light. FLU regulatory protein is located in thylakoid membrane and only contains several protein-protein interaction sites without catalytic activity. Mutants lacking this protein overaccumulate protochlorophyllide in the darkness. The interaction partners are unknown. The protein underwent simplification during evolution. |
Read more about this topic: Scaffold Protein
Famous quotes containing the words scaffold, protein and/or summary:
“Frankie mounted to the scaffold as calm as a girl can be,”
—Unknown. Frankie and Johnny (l. 85)
“Firm-style bean curd insoles cushion feet, absorb perspiration and provide more protein than meat or fish innersoles of twice the weight. Tofu compresses with use, becoming more pungent and flavorful. May be removed when not in use to dry or marinate. Innersoles are ready to eat after 1,200 miles of wear. Each pair provides adult protein requirement for 2 meals. Insoles are sized large to allow for snacks. Recipe booklet included.”
—Alfred Gingold, U.S. humorist. Items From Our Catalogue, “Tofu Innersoles,” Avon Books (1982)
“Product of a myriad various minds and contending tongues, compact of obscure and minute association, a language has its own abundant and often recondite laws, in the habitual and summary recognition of which scholarship consists.”
—Walter Pater (1839–1894)