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First published online October 8, 2008

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Abl and SHP-2: proliferative partners

The Abl-family tyrosine kinases (Abl and Arg) promote growth-factor-dependent cell proliferation by accelerating the G1-S transition and, in several forms of leukaemia, Abl (as the constitutively active BCR-Abl fusion protein) drives cell transformation. The tyrosine phosphatase SHP-2 is phosphorylated in BCR-Abl-transformed cells - but is it also a target of Abl and Arg during growth-factor-controlled proliferation? On page 3335, Rina Plattner and colleagues show that it is. By treating cells with a pharmacological Abl-family inhibitor or with siRNAs targeting Abl and Arg, the authors show that growth-factor-induced SHP-2 phosphorylation requires Abl kinases. SHP-2 is directly phosphorylated by Abl kinases at Y580 in growth-factor-stimulated cells, they show, which leads to sustained activation of ERK kinases; moreover, a constitutively active mutant of SHP-2 rescues the G1-S transition in Abl-Arg-null fibroblasts. The authors identify two further SHP-2 tyrosine residues (Y63 and Y279) that are indirectly phosphorylated by Abl kinases - notably, phosphorylation at Y63 potentiates ERK activation and cell proliferation, but phosphorylation at Y279 has the opposite effect. SHP-2, therefore, is an important mediator of Abl-kinase-dependent cell proliferation in response to growth factors.

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Related articles in JCS:

SHP-2 is a novel target of Abl kinases during cell proliferation

Sayan Mitra, Carol Beach, Gen-Sheng Feng, and Rina Plattner
JCS 2008 121: 3335-3346. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?