Differential modulation of cardiac potassium channels by Grb adaptor proteins

Ureche, Oana N.; Ureche, Liviu; Henrion, Ulrike; Strutz‐Seebohm, Nathalie; Bundis, Florian; Steinmeyer, Klaus; Läng, Florian; Seebohm, Guiscard

doi:10.1016/j.bbrc.2009.04.035

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…Differential modulation of cardiac potassium channels by Grb7 and 10 has also recently been reported (Ureche et al, 2009), however the effect of Grb14 and individual domain(s) on these channels has not been studied. To determine whether Grb7 and Grb10 have any suppressive effect on CNGA1 function, HEK-293T cells were transiently co-expressed with Myc-CNGA1 and either Grb7, Grb10 or Grb14 (positive control).…”

Section: Resultsmentioning

confidence: 99%

“…It is interesting to note that E180–182 region is only present in Grb14 and is absent in Grb7 and Grb10 (Daly et al, 1996). Grb7 and Grb10 have previously been shown to differently modulate the cardiac potassium channels (Ureche et al, 2009). It is tempting to speculate that Grb7 and Grb10 may regulate other ion channels (Ureche et al, 2009) whereas Grb14 could be more specific towards cyclic nucleotide gated channels.…”

Section: Discussionmentioning

confidence: 99%

“…Grb7 and Grb10 have previously been shown to differently modulate the cardiac potassium channels (Ureche et al, 2009). It is tempting to speculate that Grb7 and Grb10 may regulate other ion channels (Ureche et al, 2009) whereas Grb14 could be more specific towards cyclic nucleotide gated channels. Interestingly, in retinal rod photoreceptors only Grb14 is expressed but not Grb7 and Grb10 (authors unpublished data).…”

Section: Discussionmentioning

confidence: 99%

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Mechanism involved in the modulation of photoreceptor-specific cyclic nucleotidegated channel by the tyrosine kinase adapter protein Grb14

et al. 2011

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We recently found that growth factor receptor-bound (Grb) protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide gated channel alpha subunit (CNGA1). Grb14 promotes the CNG channel closure through its Ras-associating (RA) domain. In this study we show that this RA domain mediated inhibition of rod CNG channel is electrostatic in nature. Grb14 competes with cGMP for the CNGA1 binding pocket and electrostatically interacts with Arg559 through a negatively charged β- turn at its RA domain. Our study shows that the three Glu residues (180–182) in Grb14 are absolutely critical for electrostatic interaction with the cGMP binding pocket and resultant inhibition. Our studies also suggest that substitution of Lys140 with Ala or in combination with polyglutamte mutants of Grb14 resulted in a significantly reduced binding with CNGA1. These results suggest that in addition to Glu180–182 and Lys140 other residues in Grb14 may likely to be involved in the electrostatic interaction with CNGA1. The RA-domain is highly conserved among the members of Grb7 family of proteins which includes Grb7, Grb10 and Grb14. Our data indicate that Grb14 only is able to modulate the channel activity, but not Grb7 and Grb10. These studies suggest the existence of a divergence in RA domains among the members of the Grb7 family.

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Section: Resultsmentioning

confidence: 99%