RGD Reference Report - Endothelin-1 mobilizes profilin-1-bound PIP2 in cardiac muscle. - Rat Genome Database

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Endothelin-1 mobilizes profilin-1-bound PIP2 in cardiac muscle.

Authors: Evans, NJ  Walker, JW 
Citation: Evans NJ and Walker JW, Exp Biol Med (Maywood). 2006 Jun;231(6):882-7.
RGD ID: 2324852
Pubmed: PMID:16741017   (View Abstract at PubMed)

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key down-stream substrate of the endothelin signaling pathway and plays a role in regulating protein function at the membrane-cytoskeletal interface. However, the dynamic properties of distinct pools of PIP2 are poorly understood, especially for PIP2 that is bound to cytoskeletal proteins. We investigated the effects of endothelin-1 (ET-1) stimulation on protein-bound PIP2 in cardiac muscle. Isolated rat myocytes and homogenized mouse ventricles were exposed to 10 nM ET-1 for varying time periods and protein-bound PIP2 was analyzed using an anti-PIP2 antibody and Western blotting. Several cytoskeletal proteins were found to contain tightly bound PIP2, including profilin-1 (approximately 15 kDa), capZ (approximately 32 kDa), gCap39, (approximately 39 kDa) and alpha-actinin (approximately 106 kDa). Interestingly, ET-1 pretreatment reduced the amount of PIP2 bound to profilin-1 by 46% after 15 mins, followed by a recovery to near basal levels after 60 mins. ET-1 had no effect on capZ-, gCap39-, or alpha-actinin-bound PIP2 levels. To further explore the dynamics of PIP2 binding, brefeldin-A (BFA) was used to disrupt PIP2 binding to ADP-ribosylation factors and to impair receptor internalization. Pretreatment with 1 microM BFA increased the PIP2 signal on profilin-1 x 54% after 15 mins, followed by a decline to subbasal levels after 60 mins. Like ET-1, BFA had no effect on levels of PIP2 bound to capZ or to alpha-actinin. Taken together, the data indicate that profilin-1 binds PIP2 dynamically and may serve as a key regulator of the balance between cytoskeletal integrity and PIP2 availability for Ca2+/PKC signaling in the heart.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phosphatidylinositol-4,5-bisphosphate binding  IDA 2324852 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pfn1  (profilin 1)


Additional Information