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.[2]
Interactions
Signal transducing adaptor molecule has been shown to interact with
↑Takeshita T, Arita T, Asao H, Tanaka N, Higuchi M, Kuroda H, Kaneko K, Munakata H, Endo Y, Fujita T, Sugamura K (August 1996). "Cloning of a novel signal-transducing adaptor molecule containing an SH3 domain and ITAM". Biochemical and Biophysical Research Communications. 225 (3): 1035–9. doi:10.1006/bbrc.1996.1290. PMID8780729.
↑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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
↑Asao H, Sasaki Y, Arita T, Tanaka N, Endo K, Kasai H, Takeshita T, Endo Y, Fujita T, Sugamura K (December 1997). "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. doi:10.1074/jbc.272.52.32785. PMID9407053.
↑Bache KG, Raiborg C, Mehlum A, Stenmark H (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". The Journal of Biological Chemistry. 278 (14): 12513–21. doi:10.1074/jbc.M210843200. PMID12551915.
↑Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, Tanaka N, Murata K, Ishii N, Sugamura K (April 1997). "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. doi:10.1016/S1074-7613(00)80288-5. PMID9133424.
↑Kato M, Miyazawa K, Kitamura N (December 2000). "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. doi:10.1074/jbc.M007251200. PMID10982817.
↑Tanaka N, Kaneko K, Asao H, Kasai H, Endo Y, Fujita T, Takeshita T, Sugamura K (July 1999). "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. doi:10.1074/jbc.274.27.19129. PMID10383417.
↑Blackstone C, Roberts RG, Seeburg DP, Sheng M (May 2003). "Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1". Biochemical and Biophysical Research Communications. 305 (2): 345–52. doi:10.1016/S0006-291X(03)00767-8. PMID12745081.
Further reading
Takeshita T, Arita T, Higuchi M, Asao H, Endo K, Kuroda H, Tanaka N, Murata K, Ishii N, Sugamura K (April 1997). "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. doi:10.1016/S1074-7613(00)80288-5. PMID9133424.
Asao H, Sasaki Y, Arita T, Tanaka N, Endo K, Kasai H, Takeshita T, Endo Y, Fujita T, Sugamura K (December 1997). "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. doi:10.1074/jbc.272.52.32785. PMID9407053.
Tanaka N, Kaneko K, Asao H, Kasai H, Endo Y, Fujita T, Takeshita T, Sugamura K (July 1999). "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. doi:10.1074/jbc.274.27.19129. PMID10383417.
Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K (July 2000). "STAM2, a new member of the STAM family, binding to the Janus kinases". FEBS Letters. 477 (1–2): 55–61. doi:10.1016/S0014-5793(00)01760-9. PMID10899310.
Kato M, Miyazawa K, Kitamura N (December 2000). "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. doi:10.1074/jbc.M007251200. PMID10982817.
Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, Mann M, Lodish HF (December 2000). "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. doi:10.1074/jbc.M007849200. PMID10993906.
Steen H, Kuster B, Fernandez M, Pandey A, Mann M (January 2002). "Tyrosine phosphorylation mapping of the epidermal growth factor receptor signaling pathway". The Journal of Biological Chemistry. 277 (2): 1031–9. doi:10.1074/jbc.M109992200. PMID11687594.
Bache KG, Raiborg C, Mehlum A, Stenmark H (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". The Journal of Biological Chemistry. 278 (14): 12513–21. doi:10.1074/jbc.M210843200. PMID12551915.
Blackstone C, Roberts RG, Seeburg DP, Sheng M (May 2003). "Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1". Biochemical and Biophysical Research Communications. 305 (2): 345–52. doi:10.1016/S0006-291X(03)00767-8. PMID12745081.
Mizuno E, Kawahata K, Okamoto A, Kitamura N, Komada M (March 2004). "Association with Hrs is required for the early endosomal localization, stability, and function of STAM". Journal of Biochemistry. 135 (3): 385–96. doi:10.1093/jb/mvh046. PMID15113837.
Kobayashi H, Tanaka N, Asao H, Miura S, Kyuuma M, Semura K, Ishii N, Sugamura K (March 2005). "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. doi:10.1074/jbc.M409969200. PMID15640163.
Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM (September 2005). "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. doi:10.1074/mcp.M500089-MCP200. PMID15951569.
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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.