Design and Synthesis of 4-(α-Hydroxymalonyl)phenylalanine as a New Phosphotyrosyl Mimetic and Its Use in Growth Factor Receptor Bound 2 Src-Homology 2 (Grb2 SH2) Domain-Binding Peptides

2005 ◽  
Vol 48 (16) ◽  
pp. 5369-5372 ◽  
Author(s):  
Sang-Uk Kang ◽  
Karen M. Worthy ◽  
Lakshman K. Bindu ◽  
Manchao Zhang ◽  
Dajun Yang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Design And Synthesis ◽  
Src Homology 2 ◽  
Src Homology ◽  
Binding Peptides ◽  
Growth Factor Receptor Bound

Nuclear Magnetic Resonance Solution Structure of the Growth Factor Receptor-Bound Protein 2 Src Homology 2 Domain

Biochemistry ◽  
1996 ◽  
Vol 35 (36) ◽  
pp. 11852-11864 ◽  
Author(s):  
Kevin H. Thornton ◽  
W. Tom Mueller ◽  
Patrick McConnell ◽  
Guochang Zhu ◽  
Alan R. Saltiel ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Growth Factor ◽  
Magnetic Resonance ◽  
Solution Structure ◽  
Growth Factor Receptor ◽  
Src Homology 2 ◽  
Resonance Solution ◽  
Src Homology ◽  
Src Homology 2 Domain ◽  
Growth Factor Receptor Bound

scholarly journals Selectivity and Mechanism of Action of a Growth Factor Receptor-Bound Protein 2 Src Homology 2 Domain Binding Antagonist

2008 ◽  
Vol 51 (23) ◽  
pp. 7459-7468 ◽  
Author(s):  
Alessio Giubellino ◽  
Zhen-Dan Shi ◽  
Lisa M. Miller Jenkins ◽  
Karen M. Worthy ◽  
Lakshman K. Bindu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mechanism Of Action ◽  
Growth Factor Receptor ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain ◽  
Growth Factor Receptor Bound

scholarly journals Dynamic multi-site phosphorylation by Fyn and Abl drives the interaction between CRKL and the novel scaffolding receptors DCBLD1 and DCBLD2

2017 ◽  
Vol 474 (23) ◽  
pp. 3963-3984 ◽  
Author(s):  
Anna M. Schmoker ◽  
Jaye L. Weinert ◽  
Kyle J. Kellett ◽  
Hannah E. Johnson ◽  
Ryan M. Joy ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Performance ◽  
Biological Activities ◽  
Family Members ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Src Homology 2 ◽  
Negative Role ◽  
Src Homology ◽  
Epidermal Growth

Discoidin, CUB, and LCCL domain containing 2 (DCBLD2) is a neuropilin-like transmembrane scaffolding receptor with known and anticipated roles in vascular remodeling and neuronal positioning. DCBLD2 is also up-regulated in several cancers and can drive glioblastomas downstream of activated epidermal growth factor receptor. While a few studies have shown either a positive or negative role for DCBLD2 in regulating growth factor receptor signaling, little is known about the conserved signaling features of DCBLD family members that drive their molecular activities. We previously identified DCBLD2 tyrosine phosphorylation sites in intracellular YxxP motifs that are required for the phosphorylation-dependent binding of the signaling adaptors CRK and CRKL (CT10 regulator of kinase and CRK-like). These intracellular YxxP motifs are highly conserved across vertebrates and between DCBLD family members. Here, we demonstrate that, as for DCBLD2, DCBLD1 YxxP motifs are required for CRKL–SH2 (Src homology 2) binding. We report that Src family kinases (SFKs) and Abl differentially promote the interaction between the CRKL–SH2 domain and DCBLD1 and DCBLD2, and while SFKs and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL–SH2 domain, the effect of Abl is more pronounced for DCBLD1. Using high-performance liquid chromatography coupled with tandem mass spectrometry, we quantified phosphorylation at several YxxP sites in DCBLD1 and DCBLD2, mapping site-specific preferences for SFKs and Abl. Together, these data provide a platform to decipher the signaling mechanisms by which these novel receptors drive their biological activities.

scholarly journals A region of the 85-kilodalton (kDa) subunit of phosphatidylinositol 3-kinase binds the 110-kDa catalytic subunit in vivo.

1993 ◽  
Vol 13 (9) ◽  
pp. 5560-5566 ◽  
Author(s):  
A Klippel ◽  
J A Escobedo ◽  
Q Hu ◽  
L T Williams
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Catalytic Subunit ◽  
Phosphatidylinositol 3 Kinase ◽  
Region Gene ◽  
Sh2 Domains ◽  
Src Homology 2 ◽  
Src Homology

Phosphatidylinositol (PI) 3-kinase is a heterodimer consisting of an 85-kDa subunit (p85) and 110-kDa subunit (p110). The 85-kDa noncatalytic subunit, which contains two Src homology 2 (SH2) domains, one SH3 domain, and a domain homologous to the carboxy terminus of the breakpoint cluster region gene product, is known to mediate the association of the PI 3-kinase complex with activated growth factor receptors. We previously demonstrated that the C-terminal SH2 domain of p85 is responsible for the interaction of PI 3-kinase with phosphorylated platelet-derived growth factor receptor. To define the region in p85 that directs the complex formation with the PI 3-kinase catalytic subunit, a series of truncated p85 mutants was analyzed for association with p110 in vivo. We found that a fragment of p85 containing the region between the two SH2 domains was sufficient to promote the interaction with p110 in vivo. The complex between the fragment of p85 and p110 had PI 3-kinase activity that was comparable in magnitude to the activity of p110 associated with full-length p85. The binding with p110 was abolished when this domain in p85 was disrupted. These results identify a novel structural and functional element that is responsible for localizing the catalytic subunit of PI 3-kinase.

scholarly journals Inhibition of Tumor Metastasis by a Growth Factor Receptor Bound Protein 2 Src Homology 2 Domain–Binding Antagonist

2007 ◽  
Vol 67 (13) ◽  
pp. 6012-6016 ◽  
Author(s):  
Alessio Giubellino ◽  
Yang Gao ◽  
Sunmin Lee ◽  
Min-Jung Lee ◽  
James R. Vasselli ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Metastasis ◽  
Growth Factor Receptor ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain ◽  
Growth Factor Receptor Bound

Development of Non-Peptide Ligands of Growth Factor Receptor-Bound Protein 2-Src Homology 2 Domain Using Molecular Modeling and NMR Spectroscopy†

2011 ◽  
Vol 54 (4) ◽  
pp. 1096-1100 ◽  
Author(s):  
Ángel L. Orcajo-Rincón ◽  
Silvia Ortega-Gutiérrez ◽  
Pedro Serrano ◽  
Ivan R. Torrecillas ◽  
Kurt Wüthrich ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Nmr Spectroscopy ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Peptide Ligands ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain ◽  
Growth Factor Receptor Bound

A region of the 85-kilodalton (kDa) subunit of phosphatidylinositol 3-kinase binds the 110-kDa catalytic subunit in vivo

1993 ◽  
Vol 13 (9) ◽  
pp. 5560-5566
Author(s):  
A Klippel ◽  
J A Escobedo ◽  
Q Hu ◽  
L T Williams
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Catalytic Subunit ◽  
Phosphatidylinositol 3 Kinase ◽  
Region Gene ◽  
Sh2 Domains ◽  
Src Homology 2 ◽  
Src Homology

Phosphatidylinositol (PI) 3-kinase is a heterodimer consisting of an 85-kDa subunit (p85) and 110-kDa subunit (p110). The 85-kDa noncatalytic subunit, which contains two Src homology 2 (SH2) domains, one SH3 domain, and a domain homologous to the carboxy terminus of the breakpoint cluster region gene product, is known to mediate the association of the PI 3-kinase complex with activated growth factor receptors. We previously demonstrated that the C-terminal SH2 domain of p85 is responsible for the interaction of PI 3-kinase with phosphorylated platelet-derived growth factor receptor. To define the region in p85 that directs the complex formation with the PI 3-kinase catalytic subunit, a series of truncated p85 mutants was analyzed for association with p110 in vivo. We found that a fragment of p85 containing the region between the two SH2 domains was sufficient to promote the interaction with p110 in vivo. The complex between the fragment of p85 and p110 had PI 3-kinase activity that was comparable in magnitude to the activity of p110 associated with full-length p85. The binding with p110 was abolished when this domain in p85 was disrupted. These results identify a novel structural and functional element that is responsible for localizing the catalytic subunit of PI 3-kinase.

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