Protein-coding gene in the species Homo sapiens
SH2B adapter protein 2 is a protein that in humans is encoded by the SH2B2 gene .[ 5] [ 6]
Function The protein encoded by this gene is expressed in B lymphocytes and contains pleckstrin homology and src homology 2 (SH2) domains. In Burkitt lymphoma cell lines, it is tyrosine phosphorylated in response to B cell receptor stimulation. Because it binds Shc independent of stimulation and Grb2 after stimulation, it appears to play a role in signal transduction from the receptor to Shc/Grb2.[ 6]
Interactions SH2B2 has been shown to interact with TrkA [ 7] Cbl gene .[ 8] [ 9]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000160999 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005057 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Yokouchi M, Suzuki R, Masuhara M, Komiya S, Inoue A, Yoshimura A (Aug 1997). "Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation" . Oncogene . 15 (1): 7– 15. doi :10.1038/sj.onc.1201163 PMID 9233773 . ^ a b "Entrez Gene: SH2B2 SH2B adaptor protein 2" .^ Qian X, Riccio A, Zhang Y, Ginty DD (Nov 1998). "Identification and characterization of novel substrates of Trk receptors in developing neurons" . Neuron . 21 (5): 1017– 29. doi :10.1016/S0896-6273(00)80620-0 PMID 9856458 . S2CID 12354383 . ^ Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A (May 1999). "APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl" . Leukemia . 13 (5): 760– 7. doi :10.1038/sj/leu/2401397 PMID 10374881 . ^ Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J (Mar 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates" . EMBO J . 27 (5): 804– 16. doi :10.1038/emboj.2008.18 . PMC 2265755 PMID 18273061 .
Further reading
Glöckner G, Scherer S, Schattevoy R, Boright A, Weber J, Tsui LC, Rosenthal A (1998). "Large-Scale Sequencing of Two Regions in Human Chromosome 7q22: Analysis of 650 kb of Genomic Sequence around the EPO and CUTL1 Loci Reveals 17 Genes" . Genome Res . 8 (10): 1060– 73. doi :10.1101/gr.8.10.1060 . PMC 310788 PMID 9799793 . Qian X, Riccio A, Zhang Y, Ginty DD (1999). "Identification and characterization of novel substrates of Trk receptors in developing neurons" . Neuron . 21 (5): 1017– 29. doi :10.1016/S0896-6273(00)80620-0 PMID 9856458 . S2CID 12354383 . Yokouchi M, Wakioka T, Sakamoto H, Yasukawa H, Ohtsuka S, Sasaki A, Ohtsubo M, Valius M, Inoue A, Komiya S, Yoshimura A (1999). "APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis" . Oncogene . 18 (3): 759– 67. doi :10.1038/sj.onc.1202326 PMID 9989826 . Moodie SA, Alleman-Sposeto J, Gustafson TA (1999). "Identification of the APS protein as a novel insulin receptor substrate" . J. Biol. Chem . 274 (16): 11186– 93. doi :10.1074/jbc.274.16.11186 PMID 10196204 . Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A (1999). "APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl" . Leukemia . 13 (5): 760– 7. doi :10.1038/sj/leu/2401397 PMID 10374881 . Iseki M, Takaki S, Takatsu K (2000). "Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins". Biochem. Biophys. Res. Commun . 272 (1): 45– 54. doi :10.1006/bbrc.2000.2736 . PMID 10872802 . O'Brien KB, O'Shea JJ, Carter-Su C (2002). "SH2-B family members differentially regulate JAK family tyrosine kinases" . J. Biol. Chem . 277 (10): 8673– 81. doi :10.1074/jbc.M109165200 PMID 11751854 . Liu J, Kimura A, Baumann CA, Saltiel AR (2002). "APS Facilitates c-Cbl Tyrosine Phosphorylation and GLUT4 Translocation in Response to Insulin in 3T3-L1 Adipocytes" . Mol. Cell. Biol . 22 (11): 3599– 609. doi :10.1128/MCB.22.11.3599-3609.2002 . PMC 133825 PMID 11997497 . Yabana N, Shibuya M (2002). "Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity" . Oncogene . 21 (50): 7720– 9. doi :10.1038/sj.onc.1205927 PMID 12400014 . Ahn MY, Katsanakis KD, Bheda F, Pillay TS (2004). "Primary and essential role of the adaptor protein APS for recruitment of both c-Cbl and its associated protein CAP in insulin signaling" . J. Biol. Chem . 279 (20): 21526– 32. doi :10.1074/jbc.M307740200 PMID 15031295 . Wilcox A, Katsanakis KD, Bheda F, Pillay TS (2004). "Asb6, an adipocyte-specific ankyrin and SOCS box protein, interacts with APS to enable recruitment of elongins B and C to the insulin receptor signaling complex" . J. Biol. Chem . 279 (37): 38881– 8. doi :10.1074/jbc.M406101200 PMID 15231829 . Hu J, Hubbard SR (2005). "Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins" . J. Biol. Chem . 280 (19): 18943– 9. doi :10.1074/jbc.M414157200 PMID 15737992 . Iseki M, Kubo-Akashi C, Kwon SM, Yamaguchi A, Takatsu K, Takaki S (2005). "APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation". Biochem. Biophys. Res. Commun . 330 (3): 1005– 13. doi :10.1016/j.bbrc.2005.03.073 . PMID 15809095 . Katsanakis KD, Pillay TS (2006). "Cross-talk between the two divergent insulin signaling pathways is revealed by the protein kinase B (Akt)-mediated phosphorylation of adapter protein APS on serine 588" . J. Biol. Chem . 280 (45): 37827– 32. doi :10.1074/jbc.M505959200 PMID 16141217 . Li M, Li Z, Morris DL, Rui L (2007). "Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling" . Endocrinology . 148 (4): 1615– 21. doi :10.1210/en.2006-1010 . PMC 4710543 PMID 17204555 .
PDB gallery
1q2h : Phenylalanine Zipper Mediates APS Dimerization
1rpy : CRYSTAL STRUCTURE OF THE DIMERIC SH2 DOMAIN OF APS
1rqq : Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS
1v5m : Solution Structure of the Pleckstrin Homology Domain of Mouse APS
