Reactome | STAT3 is phosphorylated downstream of active ALK

STAT3 is phosphorylated downstream of active ALK

Stable Identifier

R-HSA-9701524

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

STAT3 is phosphorylated downstream of active ALK

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

STAT3 is phosphorylated at tyrosine 705 downstream of active ALK and oncogenic ALK fusion proteins and contributes to cellular survival (Zamo et al, 2002; Zhang et al, 2002; Amin et al, 2003; Chiarle et al, 2003; Chiarle et al, 2005; Sattu et al, 2013; reviewed in Turner and Alexander, 2006; Chiarle et al, 2008; Palmer et al, 2009). Whether STAT3 activation downstream of ALK is mediated directly by the receptor itself or depends on JAK3 is controversial (Zhang et al, 2002; Han et al 2006 a,b; Lai et al, 2005; Marzec et al. 2005; Shi et al, 2006; reviewed in Palmer et al, 2009). STAT3 is also phosphorylated at serine 727 in a manner that depends on the PI3K, mTOR and MAPK pathways. The functional significance of S727 phosphorylation is not entirely clear (Gambi et al, 2019). STAT3 supports cell survival by promoting the expression of a number of cell cycle and anti-apoptotic genes (reviewed in Chiarle et al, 2008).

Literature References

PubMed ID	Title	Journal	Year
11850821	Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death Zamo, A, Chiarle, R, Piva, R, Howes, J, Fan, Y, Chilosi, M, Levy, DE, Inghirami, G	Oncogene	2002
23889739	Phosphoproteomic analysis of anaplastic lymphoma kinase (ALK) downstream signaling pathways identifies signal transducer and activator of transcription 3 as a functional target of activated ALK in neuroblastoma cells Sattu, K, Hochgräfe, F, Wu, J, Umapathy, G, Schönherr, C, Ruuth, K, Chand, D, Witek, B, Fuchs, J, Li, PK, Hugosson, F, Daly, RJ, Palmer, RH, Hallberg, B	FEBS J	2013
18097461	The anaplastic lymphoma kinase in the pathogenesis of cancer Chiarle, R, Voena, C, Ambrogio, C, Piva, R, Inghirami, G	Nat. Rev. Cancer	2008
16482213	Fusion tyrosine kinase mediated signalling pathways in the transformation of haematopoietic cells Turner, SD, Alexander, DR	Leukemia	2006
15895073	Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target Chiarle, R, Simmons, WJ, Cai, H, Dhall, G, Zamo, A, Raz, R, Karras, JG, Levy, DE, Inghirami, G	Nat. Med.	2005
16170336	Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3 Marzec, M, Kasprzycka, M, Ptasznik, A, Wlodarski, P, Zhang, Q, Odum, N, Wasik, MA	Lab. Invest.	2005
16939498	JSI-124 (cucurbitacin I) inhibits Janus kinase-3/signal transducer and activator of transcription-3 signalling, downregulates nucleophosmin-anaplastic lymphoma kinase (ALK), and induces apoptosis in ALK-positive anaplastic large cell lymphoma cells Shi, X, Franko, B, Frantz, C, Amin, HM, Lai, R	Br. J. Haematol.	2006
30692217	The Transcriptional Regulator Sin3A Contributes to the Oncogenic Potential of STAT3 Gambi, G, Di Simone, E, Basso, V, Ricci, L, Wang, R, Verma, A, Elemento, O, Ponzoni, M, Inghirami, G, Icardi, L, Mondino, A	Cancer Res.	2019
16153455	Jak3 activation is significantly associated with ALK expression in anaplastic large cell lymphoma Lai, R, Rassidakis, GZ, Lin, Q, Atwell, C, Medeiros, LJ, Amin, HM	Hum. Pathol.	2005
16825495	Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma Han, Y, Amin, HM, Franko, B, Frantz, C, Shi, X, Lai, R	Blood	2006
16871283	Restoration of shp1 expression by 5-AZA-2'-deoxycytidine is associated with downregulation of JAK3/STAT3 signaling in ALK-positive anaplastic large cell lymphoma Han, Y, Amin, HM, Frantz, C, Franko, B, Lee, J, Lin, Q, Lai, R	Leukemia	2006
11751994	Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma Zhang, Q, Raghunath, PN, Xue, L, Majewski, M, Carpentieri, DF, Odum, N, Morris, S, Skorski, T, Wasik, MA	J. Immunol.	2002
12934099	Inhibition of JAK3 induces apoptosis and decreases anaplastic lymphoma kinase activity in anaplastic large cell lymphoma Amin, HM, Medeiros, LJ, Ma, Y, Feretzaki, M, Das, P, Leventaki, V, Rassidakis, GZ, O'Connor, SL, McDonnell, TJ, Lai, R	Oncogene	2003
19459784	Anaplastic lymphoma kinase: signalling in development and disease Palmer, RH, Vernersson, E, Grabbe, C, Hallberg, B	Biochem. J.	2009
12424201	NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors Chiarle, R, Gong, JZ, Guasparri, I, Pesci, A, Cai, J, Liu, J, Simmons, WJ, Dhall, G, Howes, J, Piva, R, Inghirami, G	Blood	2003