Kimberly L. Dodge-Kafka

The second messenger cAMP plays a pivotal role in the regulation of many biological processes in the heart, including calcium dynamics, contraction, and gene transcription. With an increasing number of hormones that stimulate cAMP production as well as the identification of a multitude of targets for cAMP-mediated pathways, an intriguing yet complicated question is how specificity of signaling is ensured? In other words, how does a particular hormone regulate a specific phosphorylation event when it acts via a common second messenger? The identification of scaffolding proteins that link upstream activators with their downstream targets has provided a molecular framework that allows for compartmentation of cAMP signaling pathways as well as the orchestration of spatial-temporal control over phosphorylation events.

A-Kinase Anchoring Proteins (AKAPs) are prototypical examples of scaffolding proteins that direct cAMP-responsive events while coordinating the activity of multiple signaling enzymes. AKAPs bind the regulatory subunit of the cAMP-dependent protein kinase and localize the enzyme to discrete locations within the cell. Additionally, AKAPs coordinate multiple signaling pathways through the anchoring of additional signaling enzymes such as phosphatases, phosphodiesterases, and other kinases.

My lab focuses on the characterization of AKAP signaling complexes in the heart. The first AKAP-mediated complex is found at the nuclear envelope in differentiated myocytes and is involved in the induction of cardiac hypertrophy. The second AKAP complex is found at the plasma membrane and is in a complex consisting of the b -2 adrenergic receptor, the L-type calcium channel, PDE4D3 and PKA.

Recent Publications

Dodge-Kafka, K.L., and Kapiloff, M.S. 2006. The mAKAP signaling complex: Integration of cAMP, calcium and MAP kinase signaling pathways. Eur. J. Cell Biol. (in press).

Dodge-Kafka K.L., Soughayer J., Pare G., Carlisle Michel J.J., Langeberg L.K., Kapiloff M.S., and Scott J.D. 2005. mAKAP co-ordinates two integrated cAMP effector pathways. Nature 437: 574-578.

Michel J.J., Townley, I.K., Dodge-Kafka, K.L., Zhang F., Kapiloff M.S., and Scott J.D. 2005. Spatial restriction of PDK1 activation cascades by anchoring to mAKAP alpha. Mol. Cell 20: 661-672.

Pare, G.C., Bauman, A.L., McHenry, M., Michel, J.J., Dodge-Kafka, K.L., and Kapiloff, M.S. 2005. The mAKAP complex participates in the induction of cardiac myocyte hypertrophy by adrenergic receptor signaling. J. Cell Sci. 118: 5637-5646.

Kimberly L. Dodge, Jennifer Michel Carlisle*, Ian Townley, and John D. Scott. 2004. Serine 13 on PDE4D3 increases the binding and affinity for the anchoring protein mAKAP. Biochem J. 381:587-592. *Co-first Author

Kimberly L. Dodge and John D. Scott. 2003. Calcineurin Anchoring and Cell Signaling. BBRC 311: 1111-1115.

Kimberly L. Dodge*, Mark Dell'Aqua * , Steven J. Tavalin and John D. Scott. 2002. Amino Acids 320-360 of AKAP79 are responsible for calcineurin binding. J. Biol. Chem. 277:48796-802. *Co-first Author

Kimberly L. Dodge, Samone Khouangsathiene, Michael S. Kapiloff, Robert Mouton, Elaine V. Hill, Miles D. Houslay, Lorene K. Langeberg, and John D. Scott. 2001. mAKAP asssembles a protein kinase A/PDE4 phosphodidesterase cAMP signaling module. , EMBO J. 21:1921-30.