The SH2-containing adapter protein GRB10 interacts with BCR-ABL

Bai, Ren Yuan; Jähn, Thomas; Schrem, S.; Munzert, Gerd; Weidner, K. Michael; Wang, J. Y. J.; Duyster, Justus

doi:10.1038/sj.onc.1202024

Cited by 46 publications

(47 citation statements)

References 26 publications

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“…Grb10 has also been shown to associate with several proteins including the EGF receptor (Frantz et al, 1997;He et al, 1998;Ooi et al, 1995), IR (Hansen et al, 1996;Liu and Roth, 1995;Dong et al, 1997;Frantz et al, 1997;O'Neill et al, 1996), Ret (Pandey et al, 1995), IGFR (Dey et al, 1996;He et al, 1998;Morrione et al, 1996;O'Neill et al, 1996), Elk/EphB1 (Stein et al, 1996), PDGF receptor (Frantz et al, 1997), Tek/Tie (Mano et al, 1998), Raf/MEK1 (Nantel et al, 1998), Nedd4 (Morrione et al, 1999), BCR-ABL (Bai et al, 1998), and GH receptor (Moutoussamy et al, 1998). In contrast, Grb14 has been reported to have fewer binding partners including EGFR/PDGFR (Daly et al, 1996), IR (Kasus-Jacobi et al, 1998), Tek/ Tie2 (Jones et al, 1999), FGF receptor (Reilly et al, 2000).…”

Section: Binding Partnersmentioning

confidence: 99%

The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions

2001

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Section: Binding Partnersmentioning

confidence: 99%

The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions

2001

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“…Although Grb10 interacts with tyrosine kinase receptors such as PDGF, EGF, insulin and IGF-I receptors, its function as an adapter molecule remains to be discovered (He et al, 1998;Stein et al, 1996). Indeed, Grb10 binds to signaling molecules such as Raf1, MEK1, BCR-Abl, Jak2, NEDD4 (Nantel et al, 1998;Bai et al, 1998;Moutoussamy et al, 1998;Morrione et al, 1999), but the consequences of these associations have not been elucidated. The role of Grb10 in cellular signaling is controversial.…”

Section: Introductionmentioning

confidence: 99%

The adapter protein, Grb10, is a positive regulator of vascular endothelial growth factor signaling

Giorgetti‐Peraldi

Murdaca

et al. 2001

Oncogene

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“…After 2 h, cells were lysed and Western blot with antibodies against Abl (8E9) or antiphosphotyrosine (4G10) was performed as described previously. 7 Monoclonal antiphospho-STAT5 antibodies were a kind gift from Tom Wheeler (Hamilton, New Zealand), 9 the hybridoma supernatant was diluted 1:200. Polyclonal anti-STAT5 antibodies were purchased from Santa Cruz (Heidelberg, Germany).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…7 Ba/F3 cells grown in RPMI supplemented with 10% FCS and 1 ng/ml mIL-3 were electroporated with Bcr-Ablwt and Bcr-Abl185Y393F mutant cDNAs in the MigRI vector and subsequently grown without growth factors as described previously. 8 …”

Section: Dna Constructs Cells and Transfectionsmentioning

confidence: 99%

Phosphorylation of tyrosine 393 in the kinase domain of Bcr-Abl influences the sensitivity towards imatinib in vivo

et al. 2003

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The Bcr-Abl fusion protein arising through the t(9;22)(q34;q11) reciprocal translocation is the causative agent in chronic myeloid leukemia and a subset of acute lymphocytic leukemia. Imatinib mesylate is a specific inhibitor of the Bcr-Abl kinase and has shown promising results in clinical studies. The structural relation between the Bcr-Abl oncogene and the tyrosine kinase inhibitor imatinib has recently been elucidated by an elegant crystal structure analysis, emphasizing the importance of dephosphorylated tyrosine 393 (Tyr393) in BcrAbl for access of the inhibitor to the kinase domain. By mutating this tyrosine to phenylalanine and thereby mimicking a constitutively dephosphorylated state, we now show that Ba/ F3 cells transformed by this mutant demonstrate an increased sensitivity towards imatinib in vivo. This effect is not due to an impaired kinase activity of Bcr-Abl Y393F, since a synthetic substrate is phosphorylated with similar kinetics. Treatment of Ba/F3 cells transfected with Bcr-Abl wild type with a phosphatase inhibitor diminished the effect of imatinib, but did not influence the growth of Ba/F3 cells transfected with BcrAblY393F. The results support the findings of the crystal structure and indicate that Tyr393 indeed plays a significant role for the sensitivity of Bcr-Abl towards imatinib in vivo. These data implicate the regulation of Tyr393 phosphorylation as a potential mechanism of imatinib resistance. Leukemia (2003) IntroductionThe tyrosine kinase inhibitor imatinib has recently emerged as an important new treatment option in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph + ) acute lymphocytic leukemias (ALL) carrying the t(9;22) translocation. 1,2 Unfortunately, many patients with advanced CML and nearly all patients with ALL quickly develop resistance to imatinib treatment. [3][4][5] Imatinib has been shown to bind specifically to the nucleotide-binding pocket in the catalytic domain of Bcr-Abl. 6 Tyrosine 393 (Tyr393) is located in the activation loop of the Bcr-Abl kinase domain and has been proposed to stabilize the activation loop in the open formation when phosphorylated, thereby restricting the access of imatinib to the catalytic region and compromising its inhibitory function. Thus, phosphorylation of Tyr393 may function as a switch, regulating accessibility of imatinib to its binding site in the Bcr-Abl protein. Therefore, other molecules that are able to 'flick the switch' may influence imatinib sensitivity in a Bcr-Abl tranformed cell, and overexpression of kinases or downregulation of phosphatases targeting Tyr393 may induce imatinib resistance. As the importance of this amino acid for imatinib binding has been shown in vitro, we aimed at examining the relevance of phosphorylation of Tyr393 in vivo. We demonstrate here that a mutant Bcr-Abl imitating a constitutively dephosphorylated Tyr393 renders Ba/F3 cells more sensitive towards imatinib inhibition. Materials and methods DNA constructs, cells and transfectionsThe mutation of Tyr3...

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The SH2-containing adapter protein GRB10 interacts with BCR-ABL

Cited by 46 publications

References 26 publications

The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions

The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions

The adapter protein, Grb10, is a positive regulator of vascular endothelial growth factor signaling

Phosphorylation of tyrosine 393 in the kinase domain of Bcr-Abl influences the sensitivity towards imatinib in vivo

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