Reactome | MDK and PTN in ALK signaling

MDK and PTN in ALK signaling

Stable Identifier

R-HSA-9851151

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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The cytokines pleiotrophin (PTN) and midikine (MDK) were initially proposed to act as ligands for ALK (Stoica et al, 2001; Stoica et al, 2002; reviewed in Wellstein et al, 2012; Winkler et al, 2014; Herradon and Perez-Garcia, 2014). Binding of PTN or MDK to ALK either in cell-free assays or in intact cells was shown to stimulate signaling through IRS, SHC, PLC and PI3K and to support neurite outgrowth, growth and survival (Stoica et al, 2001; Stoica et al, 2002; reviewed in Wellstein et al, 2012; Winkler et al, 2014; Herradon and Perez-Garcia, 2014). The activating effects of PTN and MDK on the ALK receptor were not universally reproducible, however, despite eliciting similar downstream signaling to those with anti-ALK monoclonal antibodies (Mathivet et al, 2007; Moog-Lutz et al, 2005; Motegi et al, 2004; Dirks et al, 2002; Miyake et al, 2002). More recently, ALKAL1 and ALKAL2 have been identified as the physiologically relevant ALK ligands (Zhang et al, 2014; Guan et al, 2015; Reshetnyak et al, 2015; Reshetnyak et al, 2018).

Literature References

PubMed ID	Title	Journal	Year
26418745	FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase Mendoza, P, Pfeifer, K, Mohammed, A, Wolfstetter, G, Palmer, RH, Halenbeck, R, Umapathy, G, Hsu, AW, Zhang, H, Hugosson, F, Guan, J, Hallberg, B, Yamazaki, Y	Elife	2015
12185581	Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines Hakomori, Y, Sakai, R, Miyake, I, Saito, M, Gamou, T, Shinohara, A, Iwamatsu, A	Oncogene	2002
26630010	Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand-receptor interactions Bai, H, Mohanty, J, Tome, F, Shi, X, Schlessinger, J, Murray, PB, Gunel, M, Mo, ES, Reshetnyak, AV, Lax, I	Proc Natl Acad Sci U S A	2015
23889475	Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives Herradón, G, Pérez-García, C	Br. J. Pharmacol.	2014
11278720	Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin Wellstein, A, Caughey, DJ, Kuo, AH, Karavanov, A, Sunitha, I, Malerczyk, C, Aigner, A, Riegel, AT, Souttou, B, Stoica, GE, Wen, D	J Biol Chem	2001
25331893	Deorphanization of the human leukocyte tyrosine kinase (LTK) receptor by a signaling screen of the extracellular proteome Bosch, E, Bray, TL, Wang, G, Kavanaugh, WM, Halenbeck, R, Lee, E, Liu, H, Hestir, K, Pao, LI, Hsu, AW, Brace, AD, Zhang, H, Zhou, A, Williams, LT, Wong, BR	Proc Natl Acad Sci U S A	2014
12115586	Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines Fähnrich, S, Becker, E, MacLeod, RA, Lis, Y, Drexler, HG, Dirks, WG	Int J Cancer	2002
23267434	ALK receptor activation, ligands and therapeutic targeting in glioblastoma and in other cancers Wellstein, A	Front Oncol	2012
12122009	Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types Wellstein, A, Kuo, AH, Stoica, GE, Riegel, AT, Bowden, ET, Sale, EB, Powers, C	J. Biol. Chem.	2002
30061385	Identification of a biologically active fragment of ALK and LTK-Ligand 2 (augmentor-α) Tomé, F, Mohanty, J, Kaur, N, Ahmed, M, Schlessinger, J, Plotnikov, AN, Puleo, DE, Cinnaiyan, AM, Reshetnyak, AV, Lax, I, Poliakov, A	Proc Natl Acad Sci U S A	2018
24125182	The midkine family of growth factors: diverse roles in nervous system formation and maintenance Winkler, C, Yao, S	Br. J. Pharmacol.	2014
15886198	Activation and inhibition of anaplastic lymphoma kinase receptor tyrosine kinase by monoclonal antibodies and absence of agonist activity of pleiotrophin Brunet-de Carvalho, N, Bureau, J, Moog-Lutz, C, Frobert, Y, Vigny, M, Créminon, C, Degoutin, J, Gouzi, JY	J Biol Chem	2005
17904822	In contrast to agonist monoclonal antibodies, both C-terminal truncated form and full length form of Pleiotrophin failed to activate vertebrate ALK (anaplastic lymphoma kinase)? Vigny, M, Mathivet, T, Mazot, P	Cell Signal	2007