Flightless-I, a gelsolin family member and transcriptional regulator, preferentially binds directly to activated cytosolic CaMK-II.
In order to evaluate links between Ca2+/calmodulin (CaM)-dependent protein kinase type II (CaMK-II) and cell cycle progression, CaMK-II binding partners were sought in proliferating cells by epitope-tag tandem mass spectrometry. One protein identified was the gelsolin family member, flightless-I (Fli-I). Fli-I is not a CaMK-II substrate, but binds directly and preferentially to constitutively active (T287D) CaMK-II over inactive CaMK-II. Fli-I gradually enters the nucleus upon CaMK-II inhibition and is retained in the cytosol by T287D CaMK-II. CaMK-II inhibition and Fli-I overexpression suppress transcription of beta-catenin dependent transcriptional reporters, whereas Fli-I suppression enhances their transcription. These findings support a novel mechanism whereby cytosolic CaMK-II influences beta-catenin dependent gene expression through Fli-I.
Seward
Matthew E
ME
Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012, United States.
Easley
Charles A
CA
McLeod
Jamie J
JJ
Myers
Alexandra L
AL
Tombes
Robert M
RM
D021581:Active Transport, Cell Nucleus; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D051176:beta Catenin / Q000378:metabolism
C098179:FLII protein, human; D008840:Microfilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2