ALK autophosphorylation

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
ALK1 is phosphorylated on tyrosine residues in intracellular domain after ligand binding and dimerization, consistent with other receptor tyrosine kinases (Soutto et al, 2001; Stoica et al, 2002; Perez-Pinera et al, 2007; Lee et al, 2010; reviewed in Roskoski, 2013; Della Corte et al, 2018). ALK1, like other members of the insulin receptor subfamily, has a YXXXXYY motif in the activation loop. Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase (Donella-Deana et al, 2005; Tartari et al, 2007; Lee et al, 2010; reviewed in Roskoski et al, 2013). ALK also contains a number of tyrosine residues in the juxtamembrane domain region, at positions 1078, 1092, 1096, 1131, 1358, 1507 and 1604, among others (Rush et al, 2005; Kuo et al, 2007; Degoutin et al, 2007; reviewed in Roskoski, 2013). Whether phosphorylation of these residues precedes activation loop phosphorylation, as is the case for other RTKs, remains to be investigated. In addition, some sites may be phosphorylated by other cellular kinases after ALK auto-phosphorylation (reviewed in Klug et al, 2018; Roskoski, 2013).
Literature References
PubMed ID Title Journal Year
17681947 Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor protein-tyrosine phosphatase beta/zeta signaling pathway: an alternative mechanism of receptor tyrosine kinase activation

Deuel, TF, Chang, Y, Vega, JA, Zhang, W, Perez-Pinera, P

J. Biol. Chem. 2007
20632993 Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain

Lesley, SA, Jia, Y, Li, N, Michellys, PY, Lee, CC, Spraggon, G, Harris, JL, Kim, S, Ng, K, Chen, C, Ambing, E, Hua, S, Gao, MY, Sun, X

Biochem. J. 2010
17274988 ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation

Vigny, M, Degoutin, J, Gouzi, JY

FEBS Lett. 2007
15592455 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells

Polakiewicz, RD, Lee, KA, Rush, J, Comb, MJ, Zhang, H, Guo, A, Moritz, A, Spek, EJ, Goss, VL, Zha, XM

Nat. Biotechnol. 2005
16878150 Recruitment of insulin receptor substrate-1 and activation of NF-kappaB essential for midkine growth signaling through anaplastic lymphoma kinase

Kuo, AH, Stoica, GE, Riegel, AT, Wellstein, A

Oncogene 2007
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Heinrich, MC, Kent, JD, Klug, LR

Pharmacol. Ther. 2018
23201355 Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition

Roskoski, R

Pharmacol. Res. 2013
15938644 Unique substrate specificity of anaplastic lymphoma kinase (ALK): development of phosphoacceptor peptides for the assay of ALK activity

Tartari, CJ, Gunby, RH, Mologni, L, Coluccia, AM, Ferrarese, A, Scapozza, L, Cesaro, L, Donella-Deana, A, Pinna, LA, Marin, O, Gambacorti-Passerini, C

Biochemistry 2005
18070884 Characterization of some molecular mechanisms governing autoactivation of the catalytic domain of the anaplastic lymphoma kinase

Tartari, CJ, Gunby, RH, Sottocornola, R, Coluccia, AM, Scapozza, L, Cimbro, B, Donella-Deana, A, Pinna, LA, Gambacorti-Passerini, C

J. Biol. Chem. 2008
11121404 Activation of anaplastic lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway

Carvalho, NB, Raulais, D, Vigny, M, Souttou, B

J. Biol. Chem. 2001
29455642 Role and targeting of anaplastic lymphoma kinase in cancer

Troiani, T, Viscardi, G, Morgillo, F, Fasano, M, Martinelli, E, Ciardiello, F, Della Corte, CM, Di Liello, R

Mol. Cancer 2018
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
Catalyst Activity

protein tyrosine kinase activity of ligand-bound ALK dimer [plasma membrane]

This event is regulated
Orthologous Events
Cite Us!