Signal transducing adaptor molecule explained

Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene.^{[1] [2]}

Function

This gene was identified by the rapid tyrosine-phosphorylation of its product in response to cytokine stimulation. The encoded protein contains an SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). This protein associates with JAK3 and JAK2 kinases via its ITAM region, and is phosphorylated by the JAK kinases upon cytokine stimulation, which suggests the function of this protein is as an adaptor molecule involved in the downstream signaling of cytokine receptors. HGS/HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) has been found to bind and counteract the function of this protein. STAM1 contains multiple amino acid sites that are phosphorylated and ubiquitinated.^[3]

Interactions

Signal transducing adaptor molecule has been shown to interact with

• HGS,^{[4] [5] [6]}
• Janus kinase 2.^[7]
• MAP3K1,^[8]
• STAMBP,^{[9] [10]} and
• TIMM8A.^[11]

Further reading

• Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, Tanaka N, Murata K, Ishii N, Sugamura K . STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction . Immunity . 6 . 4 . 449–57 . April 1997 . 9133424 . 10.1016/S1074-7613(00)80288-5 . free .
• Asao H, Sasaki Y, Arita T, Tanaka N, Endo K, Kasai H, Takeshita T, Endo Y, Fujita T, Sugamura K . Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth . The Journal of Biological Chemistry . 272 . 52 . 32785–91 . December 1997 . 9407053 . 10.1074/jbc.272.52.32785 . free .
• Tanaka N, Kaneko K, Asao H, Kasai H, Endo Y, Fujita T, Takeshita T, Sugamura K . Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines . The Journal of Biological Chemistry . 274 . 27 . 19129–35 . July 1999 . 10383417 . 10.1074/jbc.274.27.19129 . free .
• Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K . STAM2, a new member of the STAM family, binding to the Janus kinases . FEBS Letters . 477 . 1–2 . 55–61 . July 2000 . 10899310 . 10.1016/S0014-5793(00)01760-9 . 31811757 .
• Kato M, Miyazawa K, Kitamura N . A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP . The Journal of Biological Chemistry . 275 . 48 . 37481–7 . December 2000 . 10982817 . 10.1074/jbc.M007251200 . free .
• Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, Mann M, Lodish HF . Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways . The Journal of Biological Chemistry . 275 . 49 . 38633–9 . December 2000 . 10993906 . 10.1074/jbc.M007849200 . free .
• Steen H, Kuster B, Fernandez M, Pandey A, Mann M . Tyrosine phosphorylation mapping of the epidermal growth factor receptor signaling pathway . The Journal of Biological Chemistry . 277 . 2 . 1031–9 . January 2002 . 11687594 . 10.1074/jbc.M109992200 . free .
• Bache KG, Raiborg C, Mehlum A, Stenmark H . STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes . The Journal of Biological Chemistry . 278 . 14 . 12513–21 . April 2003 . 12551915 . 10.1074/jbc.M210843200 . free .
• Blackstone C, Roberts RG, Seeburg DP, Sheng M . Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1 . Biochemical and Biophysical Research Communications . 305 . 2 . 345–52 . May 2003 . 12745081 . 10.1016/S0006-291X(03)00767-8 .
• Mizuno E, Kawahata K, Kato M, Kitamura N, Komada M . STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif . Molecular Biology of the Cell . 14 . 9 . 3675–89 . September 2003 . 12972556 . 196559 . 10.1091/mbc.E02-12-0823 .
• Mizuno E, Kawahata K, Okamoto A, Kitamura N, Komada M . Association with Hrs is required for the early endosomal localization, stability, and function of STAM . Journal of Biochemistry . 135 . 3 . 385–96 . March 2004 . 15113837 . 10.1093/jb/mvh046 .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–32 . July 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Kobayashi H, Tanaka N, Asao H, Miura S, Kyuuma M, Semura K, Ishii N, Sugamura K . Hrs, a mammalian master molecule in vesicular transport and protein sorting, suppresses the degradation of ESCRT proteins signal transducing adaptor molecule 1 and 2 . The Journal of Biological Chemistry . 280 . 11 . 10468–77 . March 2005 . 15640163 . 10.1074/jbc.M409969200 . free .
• Row PE, Clague MJ, Urbé S . Growth factors induce differential phosphorylation profiles of the Hrs-STAM complex: a common node in signalling networks with signal-specific properties . The Biochemical Journal . 389 . Pt 3 . 629–36 . August 2005 . 15828871 . 1180712 . 10.1042/BJ20050067 .
• Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM . Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules . Molecular & Cellular Proteomics . 4 . 9 . 1240–50 . September 2005 . 15951569 . 10.1074/mcp.M500089-MCP200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .

Notes and References

1. Takeshita T, Arita T, Asao H, Tanaka N, Higuchi M, Kuroda H, Kaneko K, Munakata H, Endo Y, Fujita T, Sugamura K . Cloning of a novel signal-transducing adaptor molecule containing an SH3 domain and ITAM . Biochemical and Biophysical Research Communications . 225 . 3 . 1035–9 . August 1996 . 8780729 . 10.1006/bbrc.1996.1290 .
2. Web site: Entrez Gene: STAM signal transducing adaptor molecule (SH3 domain and ITAM motif) 1.
3. Web site: STAM1 (human). 2020-10-31. www.phosphosite.org.
4. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
5. Asao H, Sasaki Y, Arita T, Tanaka N, Endo K, Kasai H, Takeshita T, Endo Y, Fujita T, Sugamura K . Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth . The Journal of Biological Chemistry . 272 . 52 . 32785–91 . December 1997 . 9407053 . 10.1074/jbc.272.52.32785 . free .
6. Bache KG, Raiborg C, Mehlum A, Stenmark H . STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes . The Journal of Biological Chemistry . 278 . 14 . 12513–21 . April 2003 . 12551915 . 10.1074/jbc.M210843200 . free .
7. Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, Tanaka N, Murata K, Ishii N, Sugamura K . STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction . Immunity . 6 . 4 . 449–57 . April 1997 . 9133424 . 10.1016/S1074-7613(00)80288-5 . free .
8. Charlaftis N, Suddason T, Wu X, Anwar S, Karin M, Gallagher E . The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines . The EMBO Journal . 33 . 21 . 2581–96 . November 2014 . 25260751 . 4282369 . 10.15252/embj.201488351 .
9. Kato M, Miyazawa K, Kitamura N . A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP . The Journal of Biological Chemistry . 275 . 48 . 37481–7 . December 2000 . 10982817 . 10.1074/jbc.M007251200 . free .
10. Tanaka N, Kaneko K, Asao H, Kasai H, Endo Y, Fujita T, Takeshita T, Sugamura K . Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines . The Journal of Biological Chemistry . 274 . 27 . 19129–35 . July 1999 . 10383417 . 10.1074/jbc.274.27.19129 . free .
11. Blackstone C, Roberts RG, Seeburg DP, Sheng M . Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1 . Biochemical and Biophysical Research Communications . 305 . 2 . 345–52 . May 2003 . 12745081 . 10.1016/S0006-291X(03)00767-8 .