Reactome | Active LTK recruits GRB2:SOS1

Active LTK recruits GRB2:SOS1

Stable Identifier

R-HSA-9842669

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

3/5

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MAPK phosphorylation is observed downstream of both activated full length LTK and activated chimeric receptors of LTK (Ueno et al, 1995; Ueno et al, 1996; Yamada et al, 2008; Farhan et al, 2010; Roll and Reuther, 2012).
Binding site studies with chimeric proteins identified two NPXY sites in LTK that appear to contribute to MAPK signaling, one at the C-terminus including the SHC-binding Y862 and one closer to the juxtamembrane region, that appears to recruit IRS1. Co-immunoprecipitation studies show that GRB2 and SOS1 are pulled down with SHC1 and the activated EGFR-LTK and CSF1R-LTK receptor chimeras (Ueno et al, 1995; Ueno et al, 1996). Mutation of the SHC binding site Y862 decreases signaling through the MAPK pathway, suggesting that the complex assembled at this docking site contributes to the phosphorylation of MAPK proteins and mitogenic signaling (Ueno et al, 1996).

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
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
22347506	ALK-activating homologous mutations in LTK induce cellular transformation Reuther, GW, Roll, JD	PLoS One	2012
20548102	MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening Farhan, H, Hauri, HP, Sharan, R, Silberberg, Y, Mitrovic, S, Zerial, M, Wendeler, MW, Fava, E	J Cell Biol	2010
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