GRAP2 explained

GRB2-related adapter protein 2 also known as GRB2-related adaptor downstream of Shc (GADS) is a 37 kDa protein that in humans is encoded by the GRAP2 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. Transcript variants utilizing alternative polyA sites exist.^[3]

Interactions

GRAP2 has been shown to interact with:

• CCNDBP1,^[4]
• CD28,^[5]
• Linker of activated T cells,^{[2] [6]}
• Lymphocyte cytosolic protein 2^{[2] [5] [6]}
• MAP4K1,^[7] and
• STAMBP.^[8]

Further reading

• Bourette RP, Arnaud S, Myles GM, Blanchet JP, Rohrschneider LR, Mouchiroud G . Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development . The EMBO Journal . 17 . 24 . 7273–81 . Dec 1998 . 9857184 . 1171073 . 10.1093/emboj/17.24.7273 .
• Liu SK, McGlade CJ . Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc . Oncogene . 17 . 24 . 3073–82 . Dec 1998 . 9872323 . 10.1038/sj.onc.1202337 . free .
• Liu SK, Fang N, Koretzky GA, McGlade CJ . The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors . Current Biology . 9 . 2 . 67–75 . Jan 1999 . 10021361 . 10.1016/S0960-9822(99)80017-7 . free . 1999CBio....9...67L .
• Law CL, Ewings MK, Chaudhary PM, Solow SA, Yun TJ, Marshall AJ, Hood L, Clark EA . GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation . The Journal of Experimental Medicine . 189 . 8 . 1243–53 . Apr 1999 . 10209041 . 2193019 . 10.1084/jem.189.8.1243 .
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–95 . Dec 1999 . 10591208 . 10.1038/990031 . 1999Natur.402..489D . free .
• Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M . GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity . The Journal of Biological Chemistry . 275 . 27 . 20942–8 . Jul 2000 . 10801854 . 10.1074/jbc.M002598200 . free .
• Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE . Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling . The Journal of Biological Chemistry . 275 . 30 . 23355–61 . Jul 2000 . 10811803 . 10.1074/jbc.M000404200 . free .
• Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA . GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28 . Journal of Immunology . 164 . 11 . 5805–14 . Jun 2000 . 10820259 . 10.4049/jimmunol.164.11.5805 . free .
• Ma W, Xia C, Ling P, Qiu M, Luo Y, Tan TH, Liu M . Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes . Oncogene . 20 . 14 . 1703–14 . Mar 2001 . 11313918 . 10.1038/sj.onc.1204224 . free .
• Poetsch A, Molday LL, Molday RS . The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes . The Journal of Biological Chemistry . 276 . 51 . 48009–16 . Dec 2001 . 11641407 . 10.1074/jbc.M108941200 . free .
• Wenzel J, Sanzenbacher R, Ghadimi M, Lewitzky M, Zhou Q, Kaplan DR, Kabelitz D, Feller SM, Janssen O . Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor . FEBS Letters . 509 . 2 . 255–62 . Dec 2001 . 11741599 . 10.1016/S0014-5793(01)03174-X . free .
• Bourgin C, Bourette RP, Arnaud S, Liu Y, Rohrschneider LR, Mouchiroud G . Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding protein during monocyte/macrophage differentiation . Molecular and Cellular Biology . 22 . 11 . 3744–56 . Jun 2002 . 11997510 . 133813 . 10.1128/MCB.22.11.3744-3756.2002 .
• Guyot B, Arnaud S, Phothirath P, Bourette RP, Grasset MF, Rigal D, Mouchiroud G . Genomic organization and restricted expression of the human Mona/Gads gene suggests regulation by two specific promoters . Gene . 290 . 1–2 . 173–9 . May 2002 . 12062812 . 10.1016/S0378-1119(02)00555-3 .
• Lindholm CK, Henriksson ML, Hallberg B, Welsh M . Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells . European Journal of Biochemistry . 269 . 13 . 3279–88 . Jul 2002 . 12084069 . 10.1046/j.1432-1033.2002.03008.x . free .
• Zhu M, Janssen E, Leung K, Zhang W . Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling . The Journal of Biological Chemistry . 277 . 48 . 46151–8 . Nov 2002 . 12359715 . 10.1074/jbc.M208946200 . free .
• Guyot B, Arnaud S, Phothirath P, Rigal D, Mouchiroud G . Upstream open reading frames regulate translation of Mona/Gads adapter mRNA in the megakaryocytic lineage . Platelets . 13 . 8 . 459–64 . Dec 2002 . 12487779 . 10.1080/0953710021000059431 . 26192685 .
• Yankee TM, Solow SA, Draves KD, Clark EA . Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways . Journal of Immunology . 170 . 1 . 349–55 . Jan 2003 . 12496419 . 10.4049/jimmunol.170.1.349 . free .

Notes and References

1. Qiu M, Hua S, Agrawal M, Li G, Cai J, Chan E, Zhou H, Luo Y, Liu M . Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1 . Biochemical and Biophysical Research Communications . 253 . 2 . 443–7 . Dec 1998 . 9878555 . 10.1006/bbrc.1998.9795 .
2. Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, Takeshita T, Tsuchiya S, Konno T, Sugamura K . Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT . The Journal of Experimental Medicine . 189 . 9 . 1383–90 . May 1999 . 10224278 . 2193052 . 10.1084/jem.189.9.1383 .
3. Web site: Entrez Gene: GRAP2 GRB2-related adaptor protein 2.
4. Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M . GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity . The Journal of Biological Chemistry . 275 . 27 . 20942–8 . Jul 2000 . 10801854 . 10.1074/jbc.M002598200 . free .
5. Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA . GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28 . Journal of Immunology . 164 . 11 . 5805–14 . Jun 2000 . 10820259 . 10.4049/jimmunol.164.11.5805. free .
6. Liu SK, Fang N, Koretzky GA, McGlade CJ . The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors . Current Biology . 9 . 2 . 67–75 . Jan 1999 . 10021361 . 10.1016/s0960-9822(99)80017-7. free . 1999CBio....9...67L .
7. Ma W, Xia C, Ling P, Qiu M, Luo Y, Tan TH, Liu M . Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes . Oncogene . 20 . 14 . 1703–14 . Mar 2001 . 11313918 . 10.1038/sj.onc.1204224 . free .
8. 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 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .