The phosphatidylinositol 3′ kinase pathway is required for the survival signal of leukocyte tyrosine kinase

Ueno, Hikaru; Honda, Hiroaki; Nakamoto, Tetsuya; Yamagata, Tetsuya; Sasaki, Ko; Miyagawa, Kiyoshi; Mitani, Kinuko; Yazaki, Yoshio; Hirai, Hisamaru

doi:10.1038/sj.onc.1201153

Cited by 32 publications

(23 citation statements)

References 19 publications

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“…Similarly, when SK-N-SH cells were stimulated with mAb16-39, p85 became associated with autophosphorylated ALK as well as with tyrosinephosphorylated proteins of 200, 130, 95 and 70 kDa, whereas tyrosine phosphorylation of p85 itself was hardly detectable. The p85 subunit is associated with autophosphorylated RTKs directly (Ueno et al, 1997) or indirectly via SH2-containing proteins such as IRS-1 (Yamada et al, 1997), Gab1/2 (Bai et al, 2000;Holgado-Madruga et al, 1997), CRKL (Sattler et al, 1997) and c-Cbl (Soltoff and Cantley, 1996). Consistently, p85 reportedly associates with p80 NPM-ALK indirectly through Gab2 and CRKL (Bai et al, 2000).…”

Section: Discussionsupporting

confidence: 49%

ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth

Motegi

Fujimoto

Kotani

et al. 2004

Journal of Cell Science

148

139

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Anaplastic lymphoma kinase (ALK) is a receptor-type protein tyrosine kinase that is expressed preferentially in neurons of the central and peripheral nervous systems at late embryonic stages. To elucidate the role of ALK in neurons, we developed an agonist monoclonal antibody (mAb) against the extracellular domain of ALK. Here we show that mAb16-39 elicits tyrosine phosphorylation of endogenously expressed ALK in human neuroblastoma (SK-N-SH) cells. Stimulation of these cells with mAb16-39 markedly induces the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), Shc, and c-Cbl and also their interaction with ALK and activation of ERK1/2. Furthermore, we show that continuous incubation with mAb16-39 induces the cell growth and neurite outgrowth of SK-N-SH cells. These responses are completely blocked by MEK inhibitor PD98059 but not by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, indicating an essential role of the mitogen-activated protein kinase (MAP kinase) signaling cascade in ALK-mediated growth and differentiation of neurons.

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Section: Discussionsupporting

confidence: 49%

ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth

Motegi

Fujimoto

Kotani

et al. 2004

Journal of Cell Science

148

139

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“…In addition to IRS-1, the docking protein Shc was shown to be utilized by LTK for signaling through the Ras pathway (44). We demonstrate here that Shc is phosphorylated by PTN signaling through ALK (Fig.…”

Section: Expression Of Alk In Different Cell Lines and Theirmentioning

confidence: 59%

Identification of Anaplastic Lymphoma Kinase as a Receptor for the Growth Factor Pleiotrophin

Stoica

Kuo

Aigner

et al. 2001

Journal of Biological Chemistry

348

311

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Pleiotrophin (PTN) is a secreted growth factor that induces neurite outgrowth and is mitogenic for fibroblasts, epithelial, and endothelial cells. During tumor growth PTN can serve as an angiogenic factor and drive tumor invasion and metastasis. To identify a receptor for PTN, we panned a phage display human cDNA library against immobilized PTN protein as a bait. From this we isolated a phage insert that was homologous to an amino acid sequence stretch in the extracellular domain (ECD) of the orphan receptor tyrosine kinase anaplastic lymphoma kinase (ALK). In parallel with PTN, ALK is highly expressed during perinatal development of the nervous system and down-modulated in the adult. Animal studies demonstrated that PTN can serve as a ratelimiting angiogenic factor during tumor growth, invasion, and metastasis (8 -12). Clinical studies showed elevated serum levels and tumor expression of PTN in samples from patients with colon, stomach, pancreatic, and breast cancer (5, 13). Furthermore, PTN has been implicated in neonatal brain development as well as in neurodegenerative disorders (reviewed in Ref. 14).Obviously, understanding of PTN-mediated signal transduction as well as identification of a receptor for PTN would enhance studies on the biology and pathology of this growth factor family. Our previous studies have shown that the activation of mitogen-activated protein kinase and PI 3-kinase pathways is required for mitogenic activity of PTN, and we had found that the adaptor molecule Shc participated in signal transduction (15). Based on the work of different laboratories in various cell types, it was hypothesized that proteins of 170 -220 kDa that are tyrosine-phosphorylated in response to PTN could be part of the receptor complex (15-17). More recently, several cell membrane-located proteins were shown to bind PTN at low affinity and serve as potential coreceptors or modulators of signal transduction (18 -21), but none of these molecules carried the hallmarks of a signal transducing receptor predicted from the earlier work.To identify a receptor for PTN, we rationalized that panning of a phage display cDNA library against immobilized PTN as a bait would allow us to isolate phage containing a ligand binding fragment of the receptor on their surface. Because of the high levels of expression of PTN during the perinatal development of the nervous system, we hypothesized that fetal brain would most likely also express a PTN receptor. We therefore panned a human fetal brain cDNA phage display library over several rounds against purified PTN that had been tested for biological activity (15). From this we isolated a phage insert homologous to an amino acid sequence stretch in the ECD of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), a recently described orphan receptor with an apparent molecular mass of

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“…Others, such as c-kit and leukocyte tyrosine kinase, might contribute to leukemia cell survival and proliferation. The overexpressed leukocyte tyrosine kinase has previously been described to be expressed in hematopoiesis and B-cell progenitors, but its expression in AML has not been studied in detail (26).…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Analysis of Genome-Wide Receptor Tyrosine Kinase Expression in Human Cancers Identifies Potential Novel Drug Targets

Müller‐Tidow¹,

Schwäble²,

Steffen³

et al. 2004

Clinical Cancer Research

103

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Novel high-throughput analyses in molecular biology allow sensitive and rapid identification of disease-related genes and drug targets. We have used quantitative real-time reverse transcription-PCR reactions (n ‫؍‬ 23,000) to analyze expression of all human receptor tyrosine kinases (n ‫؍‬ 56) in malignant tumors (n ‫؍‬ 313) of different origins and normal control samples (n ‫؍‬ 58). The different tumor types expressed very different numbers of receptor tyrosine kinases: whereas brain tumors and testicular cancer expressed 50 receptor tyrosine kinases, acute myeloid leukemia (AML) samples expressed only 20 different ones. Specimens of similar tumor origin exhibited characteristic receptor tyrosine kinase expression patterns and were grouped together in hierarchical cluster analyses. When we focused on specific tumor entities, receptor tyrosine kinases were identified that were disease and/or stage specific. Leukemic blasts from AML bone marrow samples differed significantly in receptor tyrosine kinase expression compared with normal bone marrow and purified CD34؉ cells. Among the differentially expressed receptor tyrosine kinases, we found FLT3, c-kit, CSF1 receptor, EPHB6, leukocyte tyrosine kinase, and ptk7 to be highly overexpressed in AML samples. Whereas expression changes of some of these were associated with altered differentiation patterns (e.g., CSF1 receptor), others, such as FLT3, were genuinely overexpressed in leukemic blasts. These data and the associated database (http://medweb.uni-muenster.de/institute/meda/research/) provide a comprehensive view of receptor tyrosine kinase expression in human cancer. This information can assist in the definition of novel drug targets.

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The phosphatidylinositol 3′ kinase pathway is required for the survival signal of leukocyte tyrosine kinase

Cited by 32 publications

References 19 publications

ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth

ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth

Identification of Anaplastic Lymphoma Kinase as a Receptor for the Growth Factor Pleiotrophin

High-Throughput Analysis of Genome-Wide Receptor Tyrosine Kinase Expression in Human Cancers Identifies Potential Novel Drug Targets

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