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AKAP220 Links the cAMP Signaling Pathway to Cell Adhesion
Author(s) -
Logue Jeremy S,
Scott John D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.530.10
Subject(s) - iqgap1 , microbiology and biotechnology , scaffold protein , phosphorylation , chemistry , protein kinase a , cell adhesion , signal transduction , kinase , calmodulin , cadherin , actin cytoskeleton , cytoskeleton , biology , biochemistry , cell , enzyme
A‐kinase anchoring proteins (AKAP) target the cAMP dependent protein kinase PKA to precise locations inside cells. AKAP220 has been shown previously to interact with the protein kinase GSK3β [1]. Co‐anchoring of PKA and GSK3β permits robust phosphorylation of GSK3β by PKA, inhibiting GSK3β activity. Little is known, however, regarding the biological significance of this complex and its role in inhibiting GSK3β activity. Our recent evidence suggests that AKAP220 links the cAMP signaling pathway to cell adhesion. Mass spectrometry experiments identified a potential interaction between AKAP220 and IQGAP1, an effecter of rac/cdc42 that controls cell adhesion by modulating cadherin attachment to the actin cytoskeleton [2]. We have shown by co‐immunoprecipitation that endogenous AKAP220 is in a complex with both IQGAP1 and E‐cadherin in MCF‐7 cells, and that AKAP220 colocalizes with IQGAP1 and E‐cadherin at cell‐cell junctions. Binding between IQGAP1 and its partners is often regulated by binding to calmodulin through its IQ domain [2]. We find that AKAP220 preferentially binds IQGAP1 lacking the IQ domain. IQGAP1 does not contain a site for PKA phosphorylation; however a site for GSK3 was identified and can be phosphorylated in vitro . Interestingly, the GSK3 phosphorylation site in IQGAP1 is in proximity to its cadherin binding domain. AKAP220 may therefore control cell adhesion by coordinating a novel kinase cascade that links PKA regulation of GSK3β to GSK3β regulation of IQGAP1 and cadherin. Evidence that the IQ domain of IQGAP1 regulates binding to AKAP220 also suggests that this is a calcium regulated complex.