Reactome | Autophosphorylation of LTK dimer:ALKAL1,2

Autophosphorylation of LTK dimer:ALKAL1,2

Stable Identifier

R-HSA-9842648

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

3/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Autophosphorylation of LTK dimer:ALKAL1,2

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

Upon stimulation with a ligand LTK undergoes transautophosphorylation at numerous tyrosine residues in its intracellular domain. Note that some of the initial characterization of LTK signaling was carried out prior to the identification of ALKAL1 and 2 as the physiological ligands, so these studies were conducted using chimeric proteins consisting of the transmembrane and intracellular domain of LTK fused to the extracellular ligand binding domain of well-characterized receptors such as EGFR or CSF1R (Honda et al, 1994; Ueno et al, 1995; Ueno et al, 1996, Ueno et al, 1997; Yamada et al, 2008; Zhang et al, 2014). In this context, stimulation of LTK has been demonstrated to result in phosphorylation of, minimally, Y485, Y721, Y753, Y779 and Y862; validation of the in vivo phosphorylation sites in the context of the full-length LTK receptor is still pending.

Literature References

PubMed ID	Title	Journal	Year
8910363	Growth and survival signals transmitted via two distinct NPXY motifs within leukocyte tyrosine kinase, an insulin receptor-related tyrosine kinase Yazaki, Y, Mitani, K, Miyagawa, K, Kozutsumi, H, Hirai, H, Sasaki, K, Ueno, H	J Biol Chem	1996
9223670	The phosphatidylinositol 3' kinase pathway is required for the survival signal of leukocyte tyrosine kinase Yazaki, Y, Mitani, K, Honda, H, Yamagata, T, Miyagawa, K, Hirai, H, Sasaki, K, Nakamoto, T, Ueno, H	Oncogene	1997
7650032	An epidermal growth factor receptor-leukocyte tyrosine kinase chimeric receptor generates ligand-dependent growth signals through the Ras signaling pathway Yazaki, Y, Hirano, N, Kozutsumi, H, Tanaka, T, Hirai, H, Sasaki, K, Ueno, H	J Biol Chem	1995
10445845	Heart-specific activation of LTK results in cardiac hypertrophy, cardiomyocyte degeneration and gene reprogramming in transgenic mice Yazaki, Y, Terasaki, F, Harada, K, Honda, H, Kawamura, K, Komuro, I, Hirai, H, Tanaka, Y, Ueno, H	Oncogene	1999
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
18849880	Expression of a chimeric CSF1R-LTK mediates ligand-dependent neurite outgrowth Nomura, T, Takano, K, Miyake, J, Fujita, S, Yamada, S, Miyake, M	Neuroreport	2008