Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF-dependent mitogenic signals.

Fazioli, Francesca; Minichiello, Liliana; Maťoška, Václav; Castagnino, Paola; Miki, Toru; Wong, William; Fiore, Pier Paolo Di

doi:10.1002/j.1460-2075.1993.tb06058.x

Cited by 173 publications

(211 citation statements)

References 61 publications

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“…At present, we do not know how eps8 a ects the cellular function of e3B1. We have previously demonstrated that eps8 plays a positive role in mitogenic signaling (Fazioli et al, 1993a;Matoskova et al, 1995). Therefore, we postulate that eps8 is probably a negative regulator of the growth inhibitory function of e3B1.…”

Section: Discussionmentioning

confidence: 81%

“…Emerging evidence indicates that eps8, a substrate for several receptor tyrosine kinases, is likely involved in the mitogenic signaling pathways (Fazioli et al, 1993a;Matoskova et al, 1995). To study the role of eps8 in mitogenic signaling, we have used the SH3 domain of eps8 to screen a M426 expression library for proteins that interact with eps8.…”

Section: Discussionmentioning

confidence: 99%

“…Cell lysates were prepared from 80% con¯uent cells either in lysis bu er containing 50 mM Hepes pH 7.5, 150 mM NaCl, 1% Triton, 1.5 mM MgCl 2 , 5 mM EGTA, 1% glycerol, 20 mM sodium pyrophosphate, 100 ng/ml aprotinin, 100 ng/ml leupeptin, 50 mM NaF, 2 mM phenylmethylsulfonyl¯uoride (PMSF) and 10 mM sodium vanadate (Fazioli et al, 1993a) or by the subcellular fractionation procedure (Fazioli et al, 1993b) as described. Serumstarved cell lysates were obtained from 80% con¯uent cells maintained in DMEM for 24 h.…”

Section: Protein Studiesmentioning

confidence: 99%

“…Following ligand binding and dimerization, the intrinsic protein tyrosine kinase activity of the growth factor receptor is stimulated, leading to receptor autophosphorylation and subsequent phosphorylation of speci®c cellular substrates. Using an expression cloning approach, we previously identi®ed eps8 as a substrate for the epidermal growth factor receptor (EGFR) tyrosine kinase as well as several other receptor tyrosine kinases (Fazioli et al, 1993a;Wong et al, 1994). Eps8 binds to the EGFR despite of the lack of a SH2 domain.…”

Section: Introductionmentioning

confidence: 99%

“…Overexpression of eps8 in EGFR expressing ®broblasts and hematopoietic cells enhances the mitogenic response to EGF in these cells (Fazioli et al, 1993a). In NIH3T3 ®broblasts which express low numbers of EGFR, overexpression of eps8 results in cellular transformation upon addition of EGF (Matoskova et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth

1997

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Eps8, a substrate of receptor tyrosine kinases, is an SH3 domain containing protein that plays an important role in mitogenic signaling. To determine the cellular function of eps8, we used the SH3 domain of eps8 to screen a human ®broblast M426 expression library and identi®ed, a full-length cDNA clone of 3.2 kb. We designated this clone e3B1 for eps8 SH3 domain binding protein 1. Northern analysis revealed that expression of e3B1 mRNA was ubiquitious in human tissues. The e3B1 gene encodes a SH3 domain containing protein. We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. E3B1 binds to the SH3 domain of eps8 and Abl in vitro. We also demonstrated that e3B1 associates with eps8 in vivo. Phosphatase digestion and phosphoamino acid analysis revealed that p65 e3B1 is a phosphoserine containing protein and p72 e3B1 and p68 e3B1 are hyperserine-phosphorylated form of p65 e3B1 . We further determined that the p65 e3B1 was the most abundant in serum-starved NIH/ EGFR cells. Time course studies initiated by the addition of epidermal growth factor (EGF) revealed that the p72 e3B1 started to accumulate at 4 h, peaked at 8 h and remained high until 24 h. Finally, we demonstrate that NIH/EGFR ®broblasts overexpressing e3B1 grow more slowly relative to matched controls.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Protein Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth

1997

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Protein tyrosine kinases: Structure, substrate specificity, and drug discovery

Al‐Obeidi¹,

Wu²,

Lam

1998

Biopolymers

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Protein tyrosine kinases (PTKs) play a crucial role in many cell regulatory processes. It is therefore not surprising to see that functional perturbation of PTKs results in many diseases. Despite the diverse primary structure organization of various PTKs, the catalytic or kinase domains of various PTKs as well as that of Ser/Thr kinases are generally conserved. The high resolution crystal structure of a few PTKs has been solved in the last few years. In contrast to the well‐defined linear peptide substrate motifs recognized by specific Ser/Thr kinases, the identification of specific substrate motifs for PTK has been slow. It is not until recently that through the use of combinatorial peptide library methods that specific recognition motifs for specific PTKs have begun to emerge. Efficient and specific peptide substrates for some PTKs with Km at the mid μM range have been identified. Based on these peptide substrates, relatively potent (IC50 at the low μM range) and highly selective pseudosubstrate‐based peptide inhibitors have been developed. There has been enormous effort in the development of PTK inhibitors for diseases such as cancer, psoriasis, and osteoporosis. Several new high‐throughput PTK assay technologies have recently been described. Small molecules against specific PTK have been developed. Most of them are competitive inhibitors at the ATP binding site. Some of these inhibitors have already been in clinical trial. © 1998 John Wiley & Sons, Inc. Biopoly 47: 197–223, 1998

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Ectopic expression of the ErbB-3 binding protein Ebp1 inhibits growth and induces differentiation of human breast cancer cell lines

et al. 2000

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Ebp1, an ErbB-3 binding protein, translocates from the cytoplasm to the nucleus of human breast cancer cells after treatment with the ErbB-3 ligand, heregulin. The purpose of these studies was to examine the effects of ectopic expression of ebp1 on the biological properties of human ErbB-3-expressing breast carcinoma cell lines. Ectopic expression of ebp1 in ErbB-2, ErbB-3-expressing breast carcinoma cell lines resulted in inhibition of colony formation, a decreased proliferation rate, an accumulation of cells in the G2/M phase of the cell cycle, and suppression of growth in soft agar. Ectopic expression of ebp1 led to a more differentiated phenotype in AU565 breast cancer cells, as evidenced by increased expression of lipid droplets and of the milk protein casein. Basal phosphorylation of extracellular regulated kinases (Erks) 1 and 2, kinases activated by heregulin treatment, was also observed in ebp1 transfectants. The promoter for the intercellular adhesion molecule-1 gene, a heregulin-inducible gene, was constitutively activated in ebp1 transfectants as determined by reporter construct analysis. These data demonstrate that ectopic expression of the ErbB-3 binding protein Ebp1 inhibits proliferation and induces differentiation of ErbB-2, ErbB-3-expressing human breast carcinoma cell lines.

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Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF-dependent mitogenic signals.

Cited by 173 publications

References 61 publications

Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth

Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth

Protein tyrosine kinases: Structure, substrate specificity, and drug discovery

Ectopic expression of the ErbB-3 binding protein Ebp1 inhibits growth and induces differentiation of human breast cancer cell lines

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