Meltrin α cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src

Suzuki, Akiko; Kadota, Nae; Hara, Tomokazu; Nakagami, Yoshiko; Izumi, Toshiaki; Takenawa, Tadaomi; Sabe, Hisataka; Endo, Takeshi

doi:10.1038/sj.onc.1203986

Cited by 54 publications

(41 citation statements)

References 59 publications

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“…ADAM12 has been demonstrated to become phosphorylated at the C-terminal Tyr901 in vitro and in cultured cells by v-Src (50). In the present study, we did not determine whether ADAM12 is phosphorylated by PKC⑀.…”

Section: Figcontrasting

confidence: 42%

Regulation of ADAM12 Cell-surface Expression by Protein Kinase C ϵ

Sundberg

Thodeti

Kveiborg

et al. 2004

Journal of Biological Chemistry

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The ADAM (a disintegrin and metalloprotease) family consists of multidomain cell-surface proteins that have a major impact on cell behavior. These transmembraneanchored proteins are synthesized as proforms that have (from the N terminus): a prodomain; a metalloprotease-, disintegrin-like-, cysteine-rich, epidermal growth factor-like, and transmembrane domain; and a cytoplasmic tail. The 90-kDa mature form of human ADAM12 is generated in the trans-Golgi through cleavage of the prodomain by a furin-peptidase and is stored intracellularly until translocation to the cell surface as a constitutively active protein. However, little is known about the regulation of ADAM12 cell-surface translocation. Here, we used human RD rhabdomyosarcoma cells, which express ADAM12 at the cell surface, in a temporal pattern. We report that protein kinase C (PKC) ⑀ induces ADAM12 translocation to the cell surface and that catalytic activity of PKC⑀ is required for this translocation. Cells possess a diverse array of surface proteins, lipids, and carbohydrates that provide active gateways for the selective intake and release of molecular information, which is important in regulating cell behavior. In fact, many disease processes relate to disorganized cell-surface communication systems. ADAMs 1 belong to a large family of cell-surface proteins with over 30 members. The prototypical ADAM molecule is a transmembrane glycoprotein composed of several distinct domains, including a prodomain and a metalloprotease, disintegrin-like, cysteine-rich, epidermal growth factor-like, transmembrane, and cytoplasmic domain. ADAMs play important roles in cell adhesion, interacting with integrins and syndecans, and in the proteolysis of the ectodomains of cell-surface proteins,

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Section: Figcontrasting

confidence: 42%

Regulation of ADAM12 Cell-surface Expression by Protein Kinase C ϵ

Sundberg

Thodeti

Kveiborg

et al. 2004

Journal of Biological Chemistry

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“…The transmembrane ADAM proteins differ in their cytoplasmic domains, with several of them, such as ADAM-9, ADAM-10, ADAM-12, ADAM-15, ADAM-17, and ADAM-22 (11,12), containing proline-rich regions and tyrosine residues that provide opportunities for interactions with Src homology 3 (SH3) and SH2 domain-containing intracellular proteins such as Src, growth factor receptor binding protein 2 (Grb2), p85 (the regulatory subunit of phosphatidylinositol 3-kinase), MAD2, endophilin I, SH3PX1, and Fish (13)(14)(15)(16)(17). We have previously shown the interactions of the ADAM-15 cytoplasmic domain with the Src family protein tyrosine kinases (Lck and Hck), MAD, and adaptor protein Grb2 in hematopoietic cell types (18).…”

Section: Introductionmentioning

confidence: 99%

Distinct Functions of Natural ADAM-15 Cytoplasmic Domain Variants in Human Mammary Carcinoma

Zhong

Poghosyan

Pennington

et al. 2008

Molecular Cancer Research

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Adamalysins [a disintegrin and metalloproteinase (ADAM)] are a family of cell surface transmembrane proteins that have broad biological functions encompassing proteolysis, adhesion, and cell signal regulation. We previously showed that the cytoplasmic domain of ADAM-15 interacts with Src family protein tyrosine kinases and the adaptor protein growth factor receptor binding protein 2 (Grb2). In the present study, we have cloned and characterized four alternatively spliced forms of ADAM-15, which differ only in their cytoplasmic domains. We show that the four ADAM-15 variants were differentially expressed in human mammary carcinoma tissues compared with normal breast. The expression of the individual isoforms did not correlate with age, menopausal status, tumor size or grade, nodal status, Nottingham Prognostic Index, or steroid hormone receptor status. However, higher levels of two isoforms (ADAM-15A and ADAM-5B) were associated with poorer relapse-free survival in node-negative patients, whereas elevated ADAM-15C correlated with better relapse-free survival in node-positive, but not in node-negative, patients. The expression of ADAM-15A and ADAM-15B variants in MDA-MB-435 cells had differential effects on cell morphology, with adhesion, migration, and invasion enhanced by expression of ADAM-15A, whereas ADAM-15B led to reduced adhesion. Using glutathione S-transferase pull-down assays, we showed that the cytoplasmic domains of ADAM-15A, ADAM-15B, and ADAM-15C show equivalent abilities to interact with extracellular signal-regulated kinase and the adaptor molecules Grb2 and Tks5/Fish, but associate in an isoform-specific fashion with Nck and the Src and Brk tyrosine kinases. These data indicate that selective expression of ADAM-15 variants in breast cancers could play an important role in determining tumor aggressiveness by interplay with intracellular signaling pathways. (Mol Cancer Res 2008;6(3):383 -94)

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“…The signals that change positions in the 15 N-HSQC spectra of the Trx1 protein correspond to main chain amide groups from amino acids that interacted with the unlabeled ADAM17cyto protein. NMR experiments were performed using a Varian/Agilent Inova spectrometer operating at a 1 H Larmor frequency of 599,887 MHz and temperature of 25°C.…”

Section: Journal Of Biological Chemistry 43073mentioning

confidence: 99%

“…The cytoplasmic domain of ADAM12 has also been described as a partner of c-Src/Yes (14,15), Grb2 (15), PI3K (16), ␣-actinin-1 (17), Tks5/ FISK (18), PACSIN3 (19), Eve-1 (20), and PKC⑀ (21). However, most of these partners are not necessarily related to the proteolytic activation.…”

Section: Adam17mentioning

confidence: 99%

“…The hydrogen proton one-dimensional spectrum was acquired to verify that the protein was structured, and two-dimensional experiments ( 15 N-HSQC) (32) were performed to identify interactions between the proteins His-Trx-1-HA and His-FLAGADAM17cyto. For this, a His-Trx-1-HA protein sample was labeled with 15 N and the His-FLAG-ADAM17cyto protein expressed in unlabeled media (LB) and titrated in different proportions (50:1, 25:1, 10:1, 5:1, 1:1, and 2:1, respectively).…”

Section: Journal Of Biological Chemistry 43073mentioning

confidence: 99%

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