Reactome | ALK autophosphorylation

ALK autophosphorylation

Stable Identifier

R-HSA-201521

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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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