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{{Infobox_gene}}
{{PBB_Controls
'''GRB2-associated-binding protein 1''' is a [[protein]] that in humans is encoded by the ''GAB1'' [[gene]].<ref name="pmid8596638">{{cite journal | vauthors = Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ | title = A Grb2-associated docking protein in EGF- and insulin-receptor signalling | journal = Nature | volume = 379 | issue = 6565 | pages = 560–4 | date = April 1996 | pmid = 8596638 | pmc = | doi = 10.1038/379560a0 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = GRB2-associated binding protein 1
| HGNCid = 4066
| Symbol = GAB1
| AltSymbols =;
| OMIM = 604439
| ECnumber = 
| Homologene = 1542
| MGIid = 108088
| GeneAtlas_image1 = PBB_GE_GAB1_207112_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005070 |text = SH3/SH2 adaptor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component =
| Process = {{GNF_GO|id=GO:0007173 |text = epidermal growth factor receptor signaling pathway}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0008286 |text = insulin receptor signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2549
    | Hs_Ensembl = ENSG00000109458
    | Hs_RefseqProtein = NP_002030
    | Hs_RefseqmRNA = NM_002039
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 144477500
    | Hs_GenLoc_end = 144610728
    | Hs_Uniprot = Q13480
    | Mm_EntrezGene = 14388
    | Mm_Ensembl = ENSMUSG00000031714
    | Mm_RefseqmRNA = NM_021356
    | Mm_RefseqProtein = NP_067331
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 83660180
    | Mm_GenLoc_end = 83776225
    | Mm_Uniprot = Q505A4
  }}
}}
'''GRB2-associated binding protein 1''', also known as '''GAB1''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The [[protein]] encoded by this [[gene]] is a member of the IRS1-like multisubstrate [[docking protein]] family. The encoded protein is an important mediator of branching tubulogenesis and plays a central role in [[cellular growth]] response, transformation and [[apoptosis]]. Two transcript variants encoding different [[isoforms]] have been found for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: GAB1 GRB2-associated binding protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2549| accessdate = }}</ref> The expression of GAB1 was also implicated in the biology of [[lymphoid leukemia|B cell malignancies]], and is regulated by [[non-coding RNA]] (miRNA) termed [[miR-150]].<ref>{{cite journal | vauthors = Mraz M, Chen L, Rassenti LZ, Ghia EM, Li H, Jepsen K, Smith EN, Messer K, Frazer KA, Kipps TJ | title = MiR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1 | journal = Blood | volume = 124 | issue = 1 | pages = 84–95 | year = 2014 | pmid = 24787006 | doi = 10.1182/blood-2013-09-527234 | pmc=4125356}}</ref>
{{PBB_Summary
 
| section_title =
== Interactions ==
| summary_text = The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. The encoded protein is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: GAB1 GRB2-associated binding protein 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2549| accessdate = }}</ref>
 
}}
GAB1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[CRKL]],<ref name = pmid10753869>{{cite journal | vauthors = Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM | title = Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL | journal = J. Biol. Chem. | volume = 275 | issue = 15 | pages = 10772–8 | date = April 2000 | pmid = 10753869 | doi =  10.1074/jbc.275.15.10772}}</ref>
* [[Grb2]],<ref name = pmid8596638 /><ref name = pmid11960376>{{cite journal | vauthors = Oneyama C, Nakano H, Sharma SV | title = UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug | journal = Oncogene | volume = 21 | issue = 13 | pages = 2037–50 | date = March 2002 | pmid = 11960376 | doi = 10.1038/sj.onc.1205271 }}</ref><ref name = pmid11314042>{{cite journal | vauthors = Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM | title = The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif | journal = Oncogene | volume = 20 | issue = 9 | pages = 1052–62 | date = March 2001 | pmid = 11314042 | doi = 10.1038/sj.onc.1204202 }}</ref>
* [[MAP3K3]],<ref name = pmid12065326>{{cite journal | vauthors = Che W, Lerner-Marmarosh N, Huang Q, Osawa M, Ohta S, Yoshizumi M, Glassman M, Lee JD, Yan C, Berk BC, Abe J | title = Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression | journal = Circ. Res. | volume = 90 | issue = 11 | pages = 1222–30 | date = June 2002 | pmid = 12065326 | doi =  10.1161/01.res.0000021127.83364.7d}}</ref>
* [[PIK3R1]],<ref name = pmid8596638/><ref name = pmid9891995>{{cite journal | vauthors = Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S | title = Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells | journal = FEBS Lett. | volume = 441 | issue = 3 | pages = 480–4 | date = December 1998 | pmid = 9891995 | doi =  10.1016/s0014-5793(98)01593-2}}</ref><ref name = pmid9658397>{{cite journal | vauthors = Rocchi S, Tartare-Deckert S, Murdaca J, Holgado-Madruga M, Wong AJ, Van Obberghen E | title = Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules | journal = Mol. Endocrinol. | volume = 12 | issue = 7 | pages = 914–23 | date = July 1998 | pmid = 9658397 | doi = 10.1210/mend.12.7.0141 }}</ref>
* [[PLCG1]]<ref name = pmid8596638/><ref name = pmid11507676>{{cite journal | vauthors = Ueno E, Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M | title = Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes | journal = Horm. Metab. Res. | volume = 33 | issue = 7 | pages = 402–6 | date = July 2001 | pmid = 11507676 | doi = 10.1055/s-2001-16227 }}</ref>  and
* [[PTPN11]].<ref name = pmid9658397/><ref name = pmid11940581>{{cite journal | vauthors = Saito Y, Hojo Y, Tanimoto T, Abe J, Berk BC | title = Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in response to platelet-derived growth factor | journal = J. Biol. Chem. | volume = 277 | issue = 26 | pages = 23216–22 | date = June 2002 | pmid = 11940581 | doi = 10.1074/jbc.M200605200 }}</ref>  
{{Div col end}}


==References==
==References==
{{reflist|2}}
{{reflist}}
 


==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Fixman ED, Holgado-Madruga M, Nguyen L, Kamikura DM, Fournier TM, Wong AJ, Park M | title = Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1 | journal = J. Biol. Chem. | volume = 272 | issue = 32 | pages = 20167–72 | year = 1997 | pmid = 9242692 | doi = 10.1074/jbc.272.32.20167 }}
| citations =
* {{cite journal | vauthors = Nguyen L, Holgado-Madruga M, Maroun C, Fixman ED, Kamikura D, Fournier T, Charest A, Tremblay ML, Wong AJ, Park M | title = Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356 | journal = J. Biol. Chem. | volume = 272 | issue = 33 | pages = 20811–9 | year = 1997 | pmid = 9252406 | doi = 10.1074/jbc.272.33.20811 }}
*{{cite journal | author=Holgado-Madruga M, Emlet DR, Moscatello DK, ''et al.'' |title=A Grb2-associated docking protein in EGF- and insulin-receptor signalling. |journal=Nature |volume=379 |issue= 6565 |pages= 560-4 |year= 1996 |pmid= 8596638 |doi= 10.1038/379560a0 }}
* {{cite journal | vauthors = Holgado-Madruga M, Moscatello DK, Emlet DR, Dieterich R, Wong AJ | title = Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 23 | pages = 12419–24 | year = 1997 | pmid = 9356464 | pmc = 24976 | doi = 10.1073/pnas.94.23.12419 }}
*{{cite journal | author=Fixman ED, Holgado-Madruga M, Nguyen L, ''et al.'' |title=Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1. |journal=J. Biol. Chem. |volume=272 |issue= 32 |pages= 20167-72 |year= 1997 |pmid= 9242692 |doi= }}
* {{cite journal | vauthors = Rocchi S, Tartare-Deckert S, Murdaca J, Holgado-Madruga M, Wong AJ, Van Obberghen E | title = Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules | journal = Mol. Endocrinol. | volume = 12 | issue = 7 | pages = 914–23 | year = 1998 | pmid = 9658397 | doi = 10.1210/mend.12.7.0141 }}
*{{cite journal | author=Nguyen L, Holgado-Madruga M, Maroun C, ''et al.'' |title=Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356. |journal=J. Biol. Chem. |volume=272 |issue= 33 |pages= 20811-9 |year= 1997 |pmid= 9252406 |doi= }}
* {{cite journal | vauthors = Qiu M, Hua S, Agrawal M, Li G, Cai J, Chan E, Zhou H, Luo Y, Liu M | title = Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1 | journal = Biochem. Biophys. Res. Commun. | volume = 253 | issue = 2 | pages = 443–7 | year = 1999 | pmid = 9878555 | doi = 10.1006/bbrc.1998.9795 }}
*{{cite journal | author=Holgado-Madruga M, Moscatello DK, Emlet DR, ''et al.'' |title=Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 23 |pages= 12419-24 |year= 1997 |pmid= 9356464 |doi= }}
* {{cite journal | vauthors = Lehr S, Kotzka J, Herkner A, Klein E, Siethoff C, Knebel B, Noelle V, Brüning JC, Klein HW, Meyer HE, Krone W, Müller-Wieland D | title = Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro | journal = Biochemistry | volume = 38 | issue = 1 | pages = 151–9 | year = 1999 | pmid = 9890893 | doi = 10.1021/bi9818265 }}
*{{cite journal | author=Rocchi S, Tartare-Deckert S, Murdaca J, ''et al.'' |title=Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules. |journal=Mol. Endocrinol. |volume=12 |issue= 7 |pages= 914-23 |year= 1998 |pmid= 9658397 |doi= }}
* {{cite journal | vauthors = Maroun CR, Holgado-Madruga M, Royal I, Naujokas MA, Fournier TM, Wong AJ, Park M | title = The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase | journal = Mol. Cell. Biol. | volume = 19 | issue = 3 | pages = 1784–99 | year = 1999 | pmid = 10022866 | pmc = 83972 | doi = }}
*{{cite journal | author=Qiu M, Hua S, Agrawal M, ''et al.'' |title=Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1. |journal=Biochem. Biophys. Res. Commun. |volume=253 |issue= 2 |pages= 443-7 |year= 1999 |pmid= 9878555 |doi= 10.1006/bbrc.1998.9795 }}
* {{cite journal | vauthors = Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, Atsumi T, Takahashi-Tezuka M, Ishihara K, Hibi M, Hirano T | title = Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors | journal = Blood | volume = 93 | issue = 6 | pages = 1809–16 | year = 1999 | pmid = 10068651 | doi =  }}
*{{cite journal | author=Lehr S, Kotzka J, Herkner A, ''et al.'' |title=Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro. |journal=Biochemistry |volume=38 |issue= 1 |pages= 151-9 |year= 1999 |pmid= 9890893 |doi= 10.1021/bi9818265 }}
* {{cite journal | vauthors = Gual P, Giordano S, Williams TA, Rocchi S, Van Obberghen E, Comoglio PM | title = Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis | journal = Oncogene | volume = 19 | issue = 12 | pages = 1509–18 | year = 2000 | pmid = 10734310 | doi = 10.1038/sj.onc.1203514 }}
*{{cite journal | author=Maroun CR, Holgado-Madruga M, Royal I, ''et al.'' |title=The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. |journal=Mol. Cell. Biol. |volume=19 |issue= 3 |pages= 1784-99 |year= 1999 |pmid= 10022866 |doi=  }}
* {{cite journal | vauthors = Braun L, Ghebrehiwet B, Cossart P | title = gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes | journal = EMBO J. | volume = 19 | issue = 7 | pages = 1458–66 | year = 2000 | pmid = 10747014 | pmc = 310215 | doi = 10.1093/emboj/19.7.1458 }}
*{{cite journal | author=Nishida K, Yoshida Y, Itoh M, ''et al.'' |title=Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors. |journal=Blood |volume=93 |issue= 6 |pages= 1809-16 |year= 1999 |pmid= 10068651 |doi= }}
* {{cite journal | vauthors = Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM | title = Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL | journal = J. Biol. Chem. | volume = 275 | issue = 15 | pages = 10772–8 | year = 2000 | pmid = 10753869 | doi = 10.1074/jbc.275.15.10772 }}
*{{cite journal | author=Gual P, Giordano S, Williams TA, ''et al.'' |title=Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis. |journal=Oncogene |volume=19 |issue= 12 |pages= 1509-18 |year= 2000 |pmid= 10734310 |doi= 10.1038/sj.onc.1203514 }}
* {{cite journal | vauthors = Lehr S, Kotzka J, Herkner A, Sikmann A, Meyer HE, Krone W, Müller-Wieland D | title = Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro | journal = Biochemistry | volume = 39 | issue = 35 | pages = 10898–907 | year = 2000 | pmid = 10978177 | doi = 10.1021/bi000982k }}
*{{cite journal | author=Braun L, Ghebrehiwet B, Cossart P |title=gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes. |journal=EMBO J. |volume=19 |issue= 7 |pages= 1458-66 |year= 2000 |pmid= 10747014 |doi= 10.1093/emboj/19.7.1458 }}
* {{cite journal | vauthors = Sachs M, Brohmann H, Zechner D, Müller T, Hülsken J, Walther I, Schaeper U, Birchmeier C, Birchmeier W | title = Essential role of Gab1 for signaling by the c-Met receptor in vivo | journal = J. Cell Biol. | volume = 150 | issue = 6 | pages = 1375–84 | year = 2000 | pmid = 10995442 | pmc = 2150711 | doi = 10.1083/jcb.150.6.1375 }}
*{{cite journal | author=Sakkab D, Lewitzky M, Posern G, ''et al.'' |title=Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. |journal=J. Biol. Chem. |volume=275 |issue= 15 |pages= 10772-8 |year= 2000 |pmid= 10753869 |doi= }}
* {{cite journal | vauthors = Yart A, Laffargue M, Mayeux P, Chretien S, Peres C, Tonks N, Roche S, Payrastre B, Chap H, Raynal P | title = A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor | journal = J. Biol. Chem. | volume = 276 | issue = 12 | pages = 8856–64 | year = 2001 | pmid = 11134009 | doi = 10.1074/jbc.M006966200 }}
*{{cite journal | author=Lehr S, Kotzka J, Herkner A, ''et al.'' |title=Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro. |journal=Biochemistry |volume=39 |issue= 35 |pages= 10898-907 |year= 2000 |pmid= 10978177 |doi= }}
* {{cite journal | vauthors = Ingham RJ, Santos L, Dang-Lawson M, Holgado-Madruga M, Dudek P, Maroun CR, Wong AJ, Matsuuchi L, Gold MR | title = The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase | journal = J. Biol. Chem. | volume = 276 | issue = 15 | pages = 12257–65 | year = 2001 | pmid = 11278704 | doi = 10.1074/jbc.M010590200 }}
*{{cite journal | author=Sachs M, Brohmann H, Zechner D, ''et al.'' |title=Essential role of Gab1 for signaling by the c-Met receptor in vivo. |journal=J. Cell Biol. |volume=150 |issue= 6 |pages= 1375-84 |year= 2000 |pmid= 10995442 |doi= }}
* {{cite journal | vauthors = Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM | title = The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif | journal = Oncogene | volume = 20 | issue = 9 | pages = 1052–62 | year = 2001 | pmid = 11314042 | doi = 10.1038/sj.onc.1204202 }}
*{{cite journal | author=Yart A, Laffargue M, Mayeux P, ''et al.'' |title=A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor. |journal=J. Biol. Chem. |volume=276 |issue= 12 |pages= 8856-64 |year= 2001 |pmid= 11134009 |doi= 10.1074/jbc.M006966200 }}
* {{cite journal | vauthors = Cunnick JM, Mei L, Doupnik CA, Wu J | title = Phosphotyrosines 627 and 659 Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2 | journal = J. Biol. Chem. | volume = 276 | issue = 26 | pages = 24380–7 | year = 2001 | pmid = 11323411 | doi = 10.1074/jbc.M010275200 }}
*{{cite journal | author=Ingham RJ, Santos L, Dang-Lawson M, ''et al.'' |title=The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase. |journal=J. Biol. Chem. |volume=276 |issue= 15 |pages= 12257-65 |year= 2001 |pmid= 11278704 |doi= 10.1074/jbc.M010590200 }}
* {{cite journal | vauthors = Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M | title = Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction | journal = Oncogene | volume = 20 | issue = 16 | pages = 1929–38 | year = 2001 | pmid = 11360177 | doi = 10.1038/sj.onc.1204290 }}
*{{cite journal | author=Lewitzky M, Kardinal C, Gehring NH, ''et al.'' |title=The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif. |journal=Oncogene |volume=20 |issue= 9 |pages= 1052-62 |year= 2001 |pmid= 11314042 |doi= 10.1038/sj.onc.1204202 }}
* {{cite journal | vauthors = Kameda H, Risinger JI, Han BB, Baek SJ, Barrett JC, Glasgow WC, Eling TE | title = Identification of epidermal growth factor receptor- Grb2-associated binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression | journal = Cell Growth Differ. | volume = 12 | issue = 6 | pages = 307–18 | year = 2001 | pmid = 11432805 | doi =  }}
*{{cite journal | author=Cunnick JM, Mei L, Doupnik CA, Wu J |title=Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2. |journal=J. Biol. Chem. |volume=276 |issue= 26 |pages= 24380-7 |year= 2001 |pmid= 11323411 |doi= 10.1074/jbc.M010275200 }}
*{{cite journal | author=Kurokawa K, Iwashita T, Murakami H, ''et al.'' |title=Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction. |journal=Oncogene |volume=20 |issue= 16 |pages= 1929-38 |year= 2001 |pmid= 11360177 |doi= 10.1038/sj.onc.1204290 }}
*{{cite journal  | author=Kameda H, Risinger JI, Han BB, ''et al.'' |title=Identification of epidermal growth factor receptor- Grb2-associated binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression. |journal=Cell Growth Differ. |volume=12 |issue= 6 |pages= 307-18 |year= 2001 |pmid= 11432805 |doi=  }}
}}
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Revision as of 00:25, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

GRB2-associated-binding protein 1 is a protein that in humans is encoded by the GAB1 gene.[1]

Function

The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. The encoded protein is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene.[2] The expression of GAB1 was also implicated in the biology of B cell malignancies, and is regulated by non-coding RNA (miRNA) termed miR-150.[3]

Interactions

GAB1 has been shown to interact with:

References

  1. ↑ 1.0 1.1 1.2 1.3 Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (April 1996). "A Grb2-associated docking protein in EGF- and insulin-receptor signalling". Nature. 379 (6565): 560–4. doi:10.1038/379560a0. PMID 8596638.
  2. ↑ "Entrez Gene: GAB1 GRB2-associated binding protein 1".
  3. ↑ Mraz M, Chen L, Rassenti LZ, Ghia EM, Li H, Jepsen K, Smith EN, Messer K, Frazer KA, Kipps TJ (2014). "MiR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1". Blood. 124 (1): 84–95. doi:10.1182/blood-2013-09-527234. PMC 4125356. PMID 24787006.
  4. ↑ Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM (April 2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869.
  5. ↑ Oneyama C, Nakano H, Sharma SV (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene. 21 (13): 2037–50. doi:10.1038/sj.onc.1205271. PMID 11960376.
  6. ↑ Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM (March 2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene. 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. PMID 11314042.
  7. ↑ Che W, Lerner-Marmarosh N, Huang Q, Osawa M, Ohta S, Yoshizumi M, Glassman M, Lee JD, Yan C, Berk BC, Abe J (June 2002). "Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression". Circ. Res. 90 (11): 1222–30. doi:10.1161/01.res.0000021127.83364.7d. PMID 12065326.
  8. ↑ Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S (December 1998). "Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells". FEBS Lett. 441 (3): 480–4. doi:10.1016/s0014-5793(98)01593-2. PMID 9891995.
  9. ↑ 9.0 9.1 Rocchi S, Tartare-Deckert S, Murdaca J, Holgado-Madruga M, Wong AJ, Van Obberghen E (July 1998). "Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules". Mol. Endocrinol. 12 (7): 914–23. doi:10.1210/mend.12.7.0141. PMID 9658397.
  10. ↑ Ueno E, Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M (July 2001). "Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes". Horm. Metab. Res. 33 (7): 402–6. doi:10.1055/s-2001-16227. PMID 11507676.
  11. ↑ Saito Y, Hojo Y, Tanimoto T, Abe J, Berk BC (June 2002). "Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in response to platelet-derived growth factor". J. Biol. Chem. 277 (26): 23216–22. doi:10.1074/jbc.M200605200. PMID 11940581.

Further reading

  • Fixman ED, Holgado-Madruga M, Nguyen L, Kamikura DM, Fournier TM, Wong AJ, Park M (1997). "Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1". J. Biol. Chem. 272 (32): 20167–72. doi:10.1074/jbc.272.32.20167. PMID 9242692.
  • Nguyen L, Holgado-Madruga M, Maroun C, Fixman ED, Kamikura D, Fournier T, Charest A, Tremblay ML, Wong AJ, Park M (1997). "Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356". J. Biol. Chem. 272 (33): 20811–9. doi:10.1074/jbc.272.33.20811. PMID 9252406.
  • Holgado-Madruga M, Moscatello DK, Emlet DR, Dieterich R, Wong AJ (1997). "Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor". Proc. Natl. Acad. Sci. U.S.A. 94 (23): 12419–24. doi:10.1073/pnas.94.23.12419. PMC 24976. PMID 9356464.
  • Rocchi S, Tartare-Deckert S, Murdaca J, Holgado-Madruga M, Wong AJ, Van Obberghen E (1998). "Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules". Mol. Endocrinol. 12 (7): 914–23. doi:10.1210/mend.12.7.0141. PMID 9658397.
  • Qiu M, Hua S, Agrawal M, Li G, Cai J, Chan E, Zhou H, Luo Y, Liu M (1999). "Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1". Biochem. Biophys. Res. Commun. 253 (2): 443–7. doi:10.1006/bbrc.1998.9795. PMID 9878555.
  • Lehr S, Kotzka J, Herkner A, Klein E, Siethoff C, Knebel B, Noelle V, Brüning JC, Klein HW, Meyer HE, Krone W, Müller-Wieland D (1999). "Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro". Biochemistry. 38 (1): 151–9. doi:10.1021/bi9818265. PMID 9890893.
  • Maroun CR, Holgado-Madruga M, Royal I, Naujokas MA, Fournier TM, Wong AJ, Park M (1999). "The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase". Mol. Cell. Biol. 19 (3): 1784–99. PMC 83972. PMID 10022866.
  • Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, Atsumi T, Takahashi-Tezuka M, Ishihara K, Hibi M, Hirano T (1999). "Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors". Blood. 93 (6): 1809–16. PMID 10068651.
  • Gual P, Giordano S, Williams TA, Rocchi S, Van Obberghen E, Comoglio PM (2000). "Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis". Oncogene. 19 (12): 1509–18. doi:10.1038/sj.onc.1203514. PMID 10734310.
  • Braun L, Ghebrehiwet B, Cossart P (2000). "gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes". EMBO J. 19 (7): 1458–66. doi:10.1093/emboj/19.7.1458. PMC 310215. PMID 10747014.
  • Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM (2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869.
  • Lehr S, Kotzka J, Herkner A, Sikmann A, Meyer HE, Krone W, Müller-Wieland D (2000). "Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro". Biochemistry. 39 (35): 10898–907. doi:10.1021/bi000982k. PMID 10978177.
  • Sachs M, Brohmann H, Zechner D, Müller T, Hülsken J, Walther I, Schaeper U, Birchmeier C, Birchmeier W (2000). "Essential role of Gab1 for signaling by the c-Met receptor in vivo". J. Cell Biol. 150 (6): 1375–84. doi:10.1083/jcb.150.6.1375. PMC 2150711. PMID 10995442.
  • Yart A, Laffargue M, Mayeux P, Chretien S, Peres C, Tonks N, Roche S, Payrastre B, Chap H, Raynal P (2001). "A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor". J. Biol. Chem. 276 (12): 8856–64. doi:10.1074/jbc.M006966200. PMID 11134009.
  • Ingham RJ, Santos L, Dang-Lawson M, Holgado-Madruga M, Dudek P, Maroun CR, Wong AJ, Matsuuchi L, Gold MR (2001). "The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase". J. Biol. Chem. 276 (15): 12257–65. doi:10.1074/jbc.M010590200. PMID 11278704.
  • Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM (2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene. 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. PMID 11314042.
  • Cunnick JM, Mei L, Doupnik CA, Wu J (2001). "Phosphotyrosines 627 and 659 Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2". J. Biol. Chem. 276 (26): 24380–7. doi:10.1074/jbc.M010275200. PMID 11323411.
  • Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M (2001). "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene. 20 (16): 1929–38. doi:10.1038/sj.onc.1204290. PMID 11360177.
  • Kameda H, Risinger JI, Han BB, Baek SJ, Barrett JC, Glasgow WC, Eling TE (2001). "Identification of epidermal growth factor receptor- Grb2-associated binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression". Cell Growth Differ. 12 (6): 307–18. PMID 11432805.
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