A short protein description with the molecular wheight, isoforms, etc...
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When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage

PTN and MK have high lysine; that could correspond to low histones

mRNA synthesis
protein synthesis
post-translational modifications


cellular localization,
biological function


In mammals PTN (pleiotrophin) also known as HB-GAM (heparin-binding growth-associated molecule) [39], OSF-1 (osteoblast-specific factor-1) [40], HARP (heparin affinity regulatory peptide) [41] and HBNF (heparin-binding neurotrophic factor) [42]; and MK (midkine) [43], also known as RIHB (retinoic acid-inducible heparin-binding protein) [44], have been postulated to be the activating ligands for ALK [6,45]. MK and PTN are small, heparin-binding growth factors implicated in diverse processes such as neural development, cell migration and angiogenesis [46,47]. The observation that PTN could function as a ligand for ALK arises from the isolation of a small portion of the extracellular region of ALK which was identified upon screening a human foetal brain phage display cDNA library for PTN-binding partners [6]. Subsequently, the PTN-related protein MK was identified as an ALK ligand. Furthermore, antibodies directed toward the ALK extracellular domain could inhibit the in vitro ligand–receptor interaction, suggesting that MK and PTN bind ALK

Anaplastic lymphoma kinase: signalling in development and disease 2009

  • Enzymes
BRENDA - The Comprehensive Enzyme Information System"URL":
KEGG Pathways"URL":
Human Metabolome Database"URL":
  • Cell signaling and Ligand transport
  • Structural proteins



The anaplastic lymphoma kinase in the pathogenesis of cancer 2008

more links

Pathobiology of ALK+ anaplastic large-cell lymphoma 2007

Signalling via dALK occurs via binding of the ligand Jeb, downstream activation of ERK and transcription of downstream target genes. Signalling via mammalian ALK is thought to occur via ligand-mediated dimerization in response to the MK and PTN ligands. ALK mediates signalling via the JAK/STAT, RAS/MAPK, PI3K and PLCγ pathways. Activation of ALK via RPTPβ/ζ, independently of direct ALK–ligand interactions has also been proposed. Lastly, ALK is proposed to function as a dependency receptor which is cleaved by caspase 3 (Casp. 3) in the absence of ligand, thereby promoting apoptosis.

Coupling histone homeostasis to centromere integrity via the ubiquitin-proteasome system 2010

Suppression of lung adenocarcinoma through menin and polycomb gene-mediated repression of growth factor pleiotrophinMenin suppresses lung cancer through PTN 2009

ALK and its ligands bear different info about AA

while ALK and MEN1 (menin) are very similar.

and lack some AA necessary for cell cycle. For that reason MEN1 is an oncosuppressor.

Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27Kip1 and p18INK4c. 2008

Menin, the product of the Men1 gene mutated in familial multiple endocrine neoplasia type 1 (MEN1), regulates transcription in differentiated cells. Menin associates with and modulates the histone methyltransferase activity of a nuclear protein complex to activate gene expression. However, menin-dependent histone methyltransferase activity in endocrine cells has not been demonstrated, and the mechanism of endocrine tumor suppression by menin remains unclear. Here, we show that menin-dependent histone methylation maintains the in vivo expression of cyclin-dependent kinase (CDK) inhibitors to prevent pancreatic islet tumors. In vivo expression of CDK inhibitors, including p27 and p18, and other cell cycle regulators is disrupted in mouse islet tumors lacking menin. Chromatin immunoprecipitation studies reveal that menin directly associates with regions of the p27 and p18 promoters and increases methylation of lysine 4 (Lys-4) in histone H3 associated with these promoters. Moreover, H3 Lys-4 methylation associated with p27 and p18 is reduced in islet tumors from Men1 mutant mice. Thus, H3 Lys-4 methylation is a crucial function of menin in islet tumor suppression. These studies suggest an epigenetic mechanism of tumor suppression: by promoting histone modifications, menin maintains transcription at multiple loci encoding cell cycle regulators essential for endocrine growth control.

Genetic and Clinical Aspects of Primary Hyperparathyroidism: Inactivation of the MEN1 Gene - A Putative Tumour Suppressor Gene

2010-09-22T09:27:07 - Gianpiero Pescarmona


Caspase-11 regulates cell migration by promoting Aip1–Cofilin-mediated actin depolymerization 2007

Blood. 2009 Aug 20;114(8):1585-95. Epub 2009 Jun 16.
The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways. 2009
Lim MS, Carlson ML, Crockett DK, Fillmore GC, Abbott DR, Elenitoba-Johnson OF, Tripp SR, Rassidakis GZ, Medeiros LJ, Szankasi P, Elenitoba-Johnson KS.

Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Constitutive expression of the chimeric NPM/ALK fusion protein encoded by the t(2;5)(p32;q35) is a key oncogenic event in the pathogenesis of most anaplastic large cell lymphomas (ALCLs). The proteomic network alterations produced by this aberration remain largely uncharacterized. Using a mass spectrometry (MS)-driven approach to identify changes in protein expression caused by the NPM/ALK fusion, we identified diverse NPM/ALK-induced changes affecting cell proliferation, ribosome synthesis, survival, apoptosis evasion, angiogenesis, and cytoarchitectural organization. MS-based findings were confirmed using Western blotting and/or immunostaining of NPM/ALK-transfected cells and ALK-deregulated lymphomas. A subset of the proteins distinguished NPM/ALK-positive ALCLs from NPM/ALK-negative ALCLs and Hodgkin lymphoma. The multiple NPM/ALK-deregulated pathways identified by MS analysis also predicted novel biologic effects of NPM/ALK expression. In this regard, we showed loss of cell adhesion as a consequence of NPM/ALK expression in a kinase-dependent manner, and sensitivity of NPM/ALK-positive ALCLs to inhibition of the RAS, p42/44ERK, and FRAP/mTOR signaling pathways. These findings reveal that the NPM/ALK alteration affects diverse cellular pathways, and provide novel insights into NPM/ALK-positive ALCL pathobiology. Our studies carry important implications for the use of MS-driven approaches for the elucidation of neoplastic pathobiology, the identification of novel diagnostic biomarkers, and pathogenetically relevant therapeutic targets.

The proteins modulated by NPM/ALK expression are

  • previously implicated in NPM/ALK signaling including
    • PI3-K,9,10,22 JAK1,10 and SRC.23
    • MAPK pathway components that were up-regulated as a consequence of constitutive NPM/ALK expression. These included MEK kinase 1 (2.4-fold), which activates ERK1/2 and JNK1-3 MAPKs, and MAPK-APK (1.9-fold), a substrate of ERK1/2 and p38 MAPK. MAP/ERK kinase kinase 3 (MKK3) and MAPK4 (p63 MAPK) were also overexpressed by 5.9- and 4.5-fold, respectively
  • new, up-regulation of receptor tyrosine kinases
    • TEK (9.1-fold)
    • the Eph family receptor protein tyrosine kinase members, Eph tyrosine kinase 2 (5-fold), EphA3 (1.6-fold), EphB1 (3.4-fold), and HEK5 (2.8-fold).
  • cytoskeletal architecture
    • RhoA and paxillin are overexpressed in NPM/ALK-transfected cells
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