Epidermal growth factor (EGF) receptor T669 peptide kinase from 3T3-L1 cells is an EGF-stimulated "MAP" kinase.

Takishima, Kunio; Griswold-Prenner, Irene; Ingebritsen, Thomas S.; Rosner, Marsha Rich

doi:10.1073/pnas.88.6.2520

Cited by 144 publications

(80 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PKC may directly mediate the Thr654 phosphorylation, whereas Thr669 is thought to be phosphorylated by ERKs (Northwood et al, 1991;Takishima et al, 1991). We note that Thr669 lies in the only ERK phosphorylation consensus in EGFR and that the EGFR threonine phosphorylation induced by GH (Huang et al, 2003) or PRL (in this study) was not inhibited by a PKC inhibitor.…”

Section: Discussionsupporting

confidence: 46%

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Huang

Jiang

et al. 2006

Oncogene

View full text Add to dashboard Cite

Prolactin (PRL) is a polypeptide hormone produced by the anterior pituitary gland and other sites that acts both systemically and locally to cause lactation and other biological effects by interacting with the PRL receptor, a Janus kinase (JAK)2-coupled cytokine receptor family member, and activating downstream signal pathways. Recent evidence suggests PRL is a player in the pathogenesis and progression of breast cancer. Epidermal growth factor (EGF) also has effects on breast tissue, working through its receptors, epidermal growth factor receptor (EGFR) and ErbB-2 (c-neu, HER2), both intrinsic tyrosine kinase growth factor receptors. EGFR promotes pubertal breast ductal morphogenesis in mice, and both EGFR and ErbB-2 are relevant in pathogenesis and behavior of breast and other human cancers. Previous studies showed that PRL and EGF synergize to enhance motility in the human breast cancer cell line, T47D. In this study, we explored crosstalk between the PRL and EGF signaling pathways in T47D cells, with an ultimate aim of understanding how these two important factors might work together in vivo to affect breast cancer behavior. Both PRL and EGF caused robust signaling in T47D cells; PRL acutely activated JAK2, signal transducer and activator of transcription-5 (STAT5), and extracellular signal-regulated kinase-1 and -2 (ERK1 and ERK2), whereas EGF caused EGFR activation and consequent src homology collagen (SHC) activation and ERK activation. Notably, PRL also caused phosphorylation of the EGFR and ErbB-2 at sites detected by PTP101, an antibody that recognizes threonine phosphorylation at consensus motifs for ERK-induced phosphorylation. PRL-induced PTP101-reactive phosphorylation was prevented by pretreatment with PD98059, an ERK pathway inhibitor. Furthermore, PRL synergized with EGF in activating SHC and ERK and transactivating a luciferase reporter driven by c-fos gene enhancer elements, suggesting that PRL allowed markedly enhanced EGF signaling. This was accompanied by substantial inhibition of EGF-induced EGFR downregulation when PRL and EGF cotreatment was compared to EGF treatment alone. This effect of PRL was abrogated by ERK pathway inhibitor pretreatment. Our data suggest that PRL synergistically augments EGF signaling in T47D breast cancer cells at least in part by lessening EGF-induced EGFR downregulation and that this effect requires PRL-induced ERK activity and threonine phosphorylation of EGFR.

show abstract

Section: Discussionsupporting

confidence: 46%

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Huang

Jiang

et al. 2006

Oncogene

View full text Add to dashboard Cite

show abstract

“…Previous reports show that the EGFR is phosphorylated on T669 after treatment with EGF, phorbol esters or thapsigargin (Takishima et al, 1988(Takishima et al, , 1991Northwood et al, 1991). This effect was shown to be mediated by ERK (Northwood et al, 1991;Takishima et al, 1991).…”

Section: P38 Phosphorylates the Egfr On Threonine 669mentioning

confidence: 99%

Cisplatin induces PKB/Akt activation and p38MAPK phosphorylation of the EGF receptor

2006

View full text Add to dashboard Cite

Cisplatin is an effective DNA-damaging antitumor agent employed for the treatment of various human cancers. In this study, we report that Cisplatin activates PKB/Akt in several cancer cell lines and that this activation is mediated by EGFR, Src and PI3-kinase. Inhibition of PI3-kinase activity decreases the survival of the cells exposed to Cisplatin, suggesting that Cisplatin-induced PKB/Akt activation may lead to Cisplatin resistance. While investigating the EGFR-dependent PKB/Akt activation in MDA-MB-468 cells, we found that the EGFR receptor undergoes a gel mobility shift upon Cisplatin treatment, which is mediated by p38MAPK . An EGFR, in which threonine 669 was mutated to alanine (A669), is phosphorylated by p38 MAPK to a much lesser extent, suggesting that threonine 669 is a p38 phosphorylation site. We found that Cisplatin induces EGFR internalization, which is mediated by p38 MAPK-dependent phosphorylation of the receptor on threonine 669. Our results identify the EGFR as a new substrate of p38 and identify threonine 669 as a new phosphorylation site that regulates EGFR internalization. Together, these results suggest that Cisplatin has side effects, which may alter the signaling pattern of cancer cells and modulate the desired effects of Cisplatin treatment.

show abstract

“…One preparation was termed EGF receptor threonine 669 kinase; it now appears to be identical to human p44/ERK1 Our studies provide direct evidence in support of the same conclusion. The sequence around serine 243, P-L-S-P, satisfies an emerging consensus for p42 and p44 MAP kinase phosphorylation sites, P-X-S/T-P (Erickson et al, 1990;Alvarez et al, 1991;Gonzalez et al, 1991;Izumi and Maller, 1991;Takishima et al, 1991;Mukhopadhyay et al, 1992). Other nonpolar residues may be able to substitute for the upstream proline (Haycock et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of c-Jun DNA binding by mitogen-activated protein kinase.

Baichwal

Ferrell

1992

MBoC

View full text Add to dashboard Cite

Here we demonstrate that partially purified Xenopus p42 mitogen-activated protein (MAP) kinase phosphorylates bacterially expressed human c-Jun at a single site, serine 243. Several lines of evidence argue that this phosphorylation is due to p42 MAP kinase itself rather than some contaminating species. Phosphorylation of serine 243 markedly decreases the binding of c-Jun to oligonucleotides containing the 12-O-tetradecanoylphorbol-13-acetate response element. These findings suggest that MAP kinase may play a role in the down-regulation of c-Jun or in the cycle of transcriptional initiation and elongation.

show abstract

Epidermal growth factor (EGF) receptor T669 peptide kinase from 3T3-L1 cells is an EGF-stimulated "MAP" kinase.

Cited by 144 publications

References 26 publications

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Cisplatin induces PKB/Akt activation and p38MAPK phosphorylation of the EGF receptor

Inhibition of c-Jun DNA binding by mitogen-activated protein kinase.

Contact Info

Product

Resources

About