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Development. November 1, 2007; 134 (22): 4119-30.

SHP-2 is required for the maintenance of cardiac progenitors.

Langdon YG , Goetz SC , Berg AE , Swanik JT , Conlon FL .

The isolation and culturing of cardiac progenitor cells has demonstrated that growth factor signaling is required to maintain cardiac cell survival and proliferation. In this study, we demonstrate in Xenopus that SHP-2 activity is required for the maintenance of cardiac precursors in vivo. In the absence of SHP-2 signaling, cardiac progenitor cells downregulate genes associated with early heart development and fail to initiate cardiac differentiation. We further show that this requirement for SHP-2 is restricted to cardiac precursor cells undergoing active proliferation. By demonstrating that SHP-2 is phosphorylated on Y542/Y580 and that it binds to FRS-2, we place SHP-2 in the FGF pathway during early embryonic heart development. Furthermore, we demonstrate that inhibition of FGF signaling mimics the cellular and biochemical effects of SHP-2 inhibition and that these effects can be rescued by constitutively active/Noonan-syndrome-associated forms of SHP-2. Collectively, these results show that SHP-2 functions within the FGF/MAPK pathway to maintain survival of proliferating populations of cardiac progenitor cells.

PubMed ID: 17928416
PMC ID: PMC2807747
Article link: Development.
Grant support: GM 00678 NIGMS NIH HHS , HL075256-01S1 NHLBI NIH HHS , P30-S045892-02 PHS HHS , R01 HL075256 NHLBI NIH HHS , R21 HL083965 NHLBI NIH HHS , R01 HL075256-04 NHLBI NIH HHS , R21 HL083965-02 NHLBI NIH HHS , P30-S045892-02 PHS HHS , R01 HL075256-04 NHLBI NIH HHS , R01 HL075256 NHLBI NIH HHS , R21 HL083965-02 NHLBI NIH HHS , HL075256-01S1 NHLBI NIH HHS , K12 GM000678 NIGMS NIH HHS , GM 00678 NIGMS NIH HHS , R21 HL083965 NHLBI NIH HHS

Genes referenced: a2m aplnr cfd darmin fgf8 mapk1 myh4 myh6 nkx2-5 nr0b2 ptpn11 sox2 tbx1 tbx20 tbx5 tpm1

Alexander, 1999, Pubmed, Xenbase[+]

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