Search results for PRKAR1A

Showing 8 results out of 8

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Types

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Protein (4 results from a total of 4)

Identifier: R-HSA-57836
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKAR1A: P10644
Identifier: R-HSA-5610408
Species: Homo sapiens
Compartment: ciliary base
Primary external reference: UniProt: PRKAR1A: P10644
Identifier: R-HSA-9713471
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKAR1A: P10644
Identifier: R-HSA-9713476
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PRKAR1A: P10644

Complex (2 results from a total of 2)

Identifier: R-HSA-9713493
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9713503
Species: Homo sapiens
Compartment: cytosol

Reaction (2 results from a total of 2)

Identifier: R-HSA-9700179
Species: Homo sapiens
Compartment: cytosol
The ALK locus is subject to chromosomal translocations and inversions that give rise to oncogenic fusion proteins in a number of different cancers. To date, ALK has been identified as a fusion partner with more than 25 proteins in cancers ranging from anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), diffuse B-cell lymphoma, neuroblastoma, rhabdomyosarcoma and inflammatory myofibroblastic tumors, among others (reviewed in Roskoski, 2013; Della Corte et al, 2018). These fusion proteins form constitutive, ligand-independent dimers by virtue of an N-terminal dimerization domain contributed by the fusion partner, and retain the intracellular region of the ALK receptor tyrosine kinase. Expression (and often overexpression) of the fusion proteins is regulated by the promoter of the fusion partner. Signaling downstream of the fusion proteins occurs through numerous pathways including the MAP kinase, PI3K and STAT cascades, among others, but the extent to which each pathway is activated downstream of the different fusions varies (Armstrong et al, 2004; reviewed in Hallberg and Palmer, 2013; Hallberg and Palmer, 2016; Della Corte et al, 2018, Roskoski, 2013).
The best characterized ALK fusion protein is NPM-ALK, which occurs in 75-80% of ALCLs, and fuses the intracellular portion of ALK with the N-terminal region of nucleophosmin, a protein involved in DNA repair, transcription and genome stability. NPM-ALK constitutively dimerizes based on the N-terminal NPM region. Deletion of the N-terminal domain abrogates oligomerization and abolishes the transformation activity of the protein (Morris et al, 1995; Fujimoto et al, 1996).
In addition to NPM, fusions with ALK have also been identified with EML4 (Soda et al, 2007; Choi et al, 2008; Takezawa et al, 2011), CLTC (De Paepe et al, 2003; Cherchetti et al, 2011; Chiakatsu et al, 2003), TPM3 (Lamant et al, 1999; Lawrence et al, 2000), TPM4 (Lawrence et al, 2000), RANBP2 (Marino-Enriquez et al, 2011a; Lee et al, 2017; Chen et al, 2008), STRN (Majewska et al, 2013; Perot et al, 2014; Kelly et al, 2014), ATIC (Colleoni et al, 2000; Trinei et al, 2000; Ma et al, 2000), KIF5B (Wong et al, 2011), TFG (Hernandez et al, 1999; Hernandez et al, 2002), HIP1 (Ou et al, 2014; Hong et al, 2014; Fang et al, 2014), CARS1 (Cools et al, 2002; Debelenko et al, 2003), PPF1BP1 (Takeuchi et al, 2011; Yoshida et al, 2013), MSN (Tort et al, 2001), VCL (Marino-Enriquez et al, 2011b; Debelenko et al, 2011), KLC1 (Togayashi et al, 2012), SEC31A (Panagopoulos et al, 2006), SQSTM1 (Iyevleva et al, 2015; Takeuchi et al, 2011), TPR (Choi et al, 2014), WDCP (Lipson et al, 2012), RRBP1 (Lee et al, 2017), DCTN1 (Subbiah et al, 2015; Lee et al, 2017; Iyevleva et al, 2015; Wang et al, 2012; Wiesner et al, 2014), EEF1A (van der Krogt et al, 2017), BIRC6 (Shan et al, 2015), EIF2AK3 (Ali et al, 2016), PPM1B (Ali et al, 2016), PRKAR1A (Ali et al, 2016), GCC2 (Noh et al, 2017), BCL11A (Tian et al, 2007) and LMO7 (Noh et al, 2017).
Identifier: R-HSA-9700131
Species: Homo sapiens
Compartment: cytosol, plasma membrane
The following ALK mutants and fusion proteins are sensitive to these type I tyrosine kinase inhibitors:
crizotinib:

ALK F1174V: Ceccon et al, 2015
ALK L1198F: Chuang et al, 2019; Ceccon et al, 2015
BCL11A(1-219)InsDHPPA-ALK(1058-1620): Tian et al, 2017
BIRC6(1-958)-ALK(1058-1620): Shan et al, 2015
EIF2AK3(30-144)-ALK(1058-1620): Ali et al, 2016
EML4(1-223)-ALK(1059-1620): Ali et al, 2016
EML4(1-223)insKMSTREKNSQV-ALK(1059-1620): Ali et al, 2016
EML4(1-486)-ALK(1058-1620): Ali et al, 2016; Hrustanovic et al, 2015; Katayama et al, 2011
FN1(32-1201)-ALK(1022-1620): Ren et al, 2012
HIP1(1-1019)-ALK(1058-1620): Ou et al, 2014
HIP1(1-963)-ALK(1058-1620): Hong et al, 2014
HIP1(1-719)InsL-ALK(1059-1620): Fang et al, 2014
NPM1(1-117)-ALK(1058-1620): Prokoph et al, 2020
PPM1B (1-282)-ALK(1058-1620): Ali et al, 2016
PRKAR1A(1-183)-ALK(1058-1620): Ali et al, 2016
STRN(1-137)-ALK(1058-1620): Kelly et al, 2014


NVP-TAE684:

ALK F1174L: George et al, 2008; Heuckmann et al, 2011
ALK V1180L: Katayama et al, 2014
ALK L1196M: Heuckmann et al, 2011
ALK L1196Q: Ceccon et al, 2013
ALK G1269S: Heuckmann, 2011
ALK R1275Q: George, 2008
CLTC(2-1634)-ALK(1059-1620): Cerchietti et al, 2011
EML4(1-223)insKMSTREKNSQV -ALK(1059-1620): Heuckmann, 2011
FN1(32-1201)-ALK(1022-1620): Ren et al, 2012
NPM1(1-117)-ALK(1058-1620): Galkin et al, 2007
STRN(1-137)-ALK(1058-1620): Kelly et al, 2014

ceritinib:

ALK I1171T: Friboulet et al, 2014; Katayama et al, 2014
ALK F1174V: Ceccon et al, 2015
ALK V1180L: Katayama et al, 2014
ALK S1206Y: Friboulet et al, 2014;
ALK G1269A: Friboulet et al, 2014;
EML4(1-486)-ALK(1058-1620): Hrustanovic et al, 2015

brigatinib:

ALK F1174V: Ceccon et al, 2015
ALK V1180L: Katayama et al, 2014
ALK L1196Q: Ceccon et al, 2013
NPM1(1-117)-ALK(1058-1620): Ceccon et al, 2015


alectinib:

ALK F1174I: Ou et al, 2016
ALK F1174L: Ou et al, 2016
ALK F1174V: Ou et al, 2016; Ceccon et al, 2015 (moderate)
EML4(1-223)-ALK(1059-1620): Ou et al, 2014
EML4(1-223)insKMSTREKNSQV-ALK(1059-1620): Ou et al, 2014
EML4(1-486)-ALK(1058-1620): Davare et al, 2015
HIP1(1-1019)-ALK(1058-1620):Ou et al, 2014

ASP3026:

ALK V1180L: Katayama et al, 2014

Entrectinib:

ALK C1156Y: Ardini et al, 2016
ALK L1196M: Ardini et al, 2016
EML4(1-223)-ALK(1059-1620): Ardini et al, 2016
EML4(1-223)insKMSTREKNSQV-ALK(1059-1620): Ardini et al, 2016
EML4(1-486)-ALK(1058-1620): Ardini et al, 2016
NPM1(1-117)-ALK(1058-1620): Ardini et al, 2016
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