The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced cell transformation.
Tel-Abl and Tel-Jak2 are fusion proteins associated with human haematologic neoplasms. They possess constitutive tyrosine kinase activity and activate common downstream signalling pathways like Stat-5, PI3-K/Akt, Ras/MapK and NF-kappaB. In this study, we showed the specific requirement of Src family members for the Tel-Abl-mediated cell growth, activation of Stat5, PI3-K/Akt and Ras/MapK while dispensable for Tel-Jak2. Hck was found strongly phosphorylated in Tel-Abl-expressing Ba/F3 cells and sensitive to imatinib mesylate treatment, providing evidence that Hck is a target of Tel-Abl tyrosine kinase activity. Overexpression of a kinase dead form of Hck inhibits the proliferation of Ba/F3 cells expressing Tel-Abl as the phosphorylation of Akt and Erk1/2. These results argue for an important role of Hck in Tel-Abl oncogenic signalling.
Pecquet
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C
INSERM, E351, 3 rue des Louvels, Université de Picardie Jules Verne, Amiens, France.
Nyga
R
R
Penard-Lacronique
V
V
Smithgall
T E
TE
Murakami
H
H
Régnier
A
A
Lassoued
K
K
Gouilleux
F
F
D001549:Benzamides; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051572:Proto-Oncogene Proteins c-hck / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D000097764:ETS Translocation Variant 6 Protein; D053614:Janus Kinase 2
D001549:Benzamides; D000068877:Imatinib Mesylate; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D051572:Proto-Oncogene Proteins c-hck; D011743:Pyrimidines; C426234:TEL-ABL fusion protein, human; D000097764:ETS Translocation Variant 6 Protein; C108603:TEL-JAK2 fusion protein, human; D053614:Janus Kinase 2; C496631:HCK protein, human