Reactome | LTK binds ALKAL ligand

LTK binds ALKAL ligand

Stable Identifier

R-HSA-9842660

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

3/5

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Leukocyte tyrosine kinase (LTK) receptor is a member of the ALK/LTK family of receptors. Although its function is not clearly defined, LTK appears to signal through the PI3K and RAS pathways, and activated LTK promotes neurite outgrowth and cell survival (Ueno et al, 1997; Yamada et al, 2008).
Signaling through LTK is stimulated by the binding of ligands ALKAL1 and ALKAL2 (also known as FAM150A and FAM150B) to the extracellular domain (Zhang et al, 2014; Guan et al, 2015; Reshetnyak et al, 2015). ALKAL1 and 2 are also able to bind and stimulate the related ALK receptor, albeit with differing affinities (ALKAL2 is a more potent ALK activator than ALKAL1, but both ligands are able to signal strongly through LTK (Reshetnyak et al, 2018)). ALKAL1 appears to bind both receptors as a monomer, but the evidence for ALKAL2 is conflicting (De Munck et al, 2021; Reshetnyak et al, 2018; Reshetnyak et al, 2021).

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
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
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
34819673	Mechanism for the activation of the anaplastic lymphoma kinase receptor Kalodimos, CG, Mohanty, J, Miller, DJ, Schlessinger, J, Reshetnyak, AV, Nourse, A, Lax, I, Sowaileh, M, Rossi, P, Myasnikov, AG	Nature	2021
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
34646012	Structural basis of cytokine-mediated activation of ALK family receptors Felix, J, Yoshimi, A, Mukohyama, J, Kurikawa, M, Provost, M, Bloch, Y, Savvides, SN, Abdel-Wahab, O, De Munck, S, Omori, I, Bazan, JF	Nature	2021
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