Filamin A in somatostatin and dopamine receptor regulation in pituitary and the role of cAMP/PKA dependent phosphorylation.

Abstract

Molecular mechanisms underlying resistance of pituitary tumors to somatostatin (SS) and dopamine (DA) analogues treatment are not completely understood. Resistance has been associated with defective expression of functional somatostatin and dopamine receptors SSTR2, SSTR5, and DRD2, respectively. Recently, a role of cytoskeleton protein filamin A (FLNA) in DRD2 and SSTR receptors expression and signaling in PRL- and GH-secreting tumors, respectively, has been demonstrated, first revealing a link between FLNA expression and responsiveness of pituitary tumors to pharmacological therapy. No molecular events underlying the reduction of FLNA levels in resistant tumors have been so far identified. FLNA can be phosphorylated by PKA on Ser2152, with increased FLNA resistance to cleavage by calpain and conformational changes affecting FLNA regions involved in SSTR2 and DRD2 binding and signal transduction. In this respect, the effect of cAMP/PKA pathway in the regulation of FLNA stability and/or function by modulating its phosphorylation status could assume particular importance in pituitary, where cAMP cascade plays a crucial role in pituitary cell functions and tumorigenesis. This review will discuss the role of FLNA in the regulation of the main GPCRs target of pharmacological treatment of pituitary tumors, that is, SSTR2 and DRD2, focusing on the effects of cAMP/PKA-mediated FLNA phosphorylation on FLNA biological functions.

• Authors: E Peverelli, E Giardino, E Vitali, D Treppiedi, A G Lania, G Mantovani
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 46 Issue 12 Pg. 845-53 (Nov 2014) ISSN: 1439-4286 [Electronic] Germany
• PMID: 25068602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Filamins
• Receptors, Dopamine
• Somatostatin
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases

Topics

• Animals
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Filamins (metabolism)
• Humans
• Phosphorylation
• Pituitary Gland (metabolism)
• Receptors, Dopamine (metabolism)
• Somatostatin (metabolism)