Edward R. Meyer Distinguished Professor School of Molecular Biosciences Washington State University Pullman, WA 99164-4234   Phone: 509-335-6658 FAX: 509-335-1907 E-mail: mehd@.wsu.edu Ph.D. University of Illinois-Urbana, 1973     RESEARCH INTERESTS: Signaling pathways by which theprototypical glycoprotein hormones follicle stimulating hormone (FSH) and lutenizing hormone (LH) signal to initiate cellular responses of differentiation and proliferation. RESEARCH SUMMARY: The focus of my lab is to elucidate thee signaling pathways by which the prototypical glycoprotein hormones follicle stimulating hormone (FSH) and lutenizing hormone (LH) signal to initiate cellular responses of differentiation and proliferaion. Our studies carried out in the native environment of the ovarian granulosa cell so that physiologically relevant data can be obtained. Both LH and FSH signal predominately via the second messenger cAMP andits targt protein kinase A (PKA). We have shon that both FSSH and LH signal via PKA to activae the MAPK/ERK pathway, althoughthe mechanism by which PKA signals into this pathway differs for LH and FSH in immature cersus matur granulosa cells. In immature granulosa cells, FSH regulates MAPK/ERK activation by regulating the association of an inhibitory protein tyrosine phosphatase with MAPK/ERK. However, regulation of this MAPK/ERK pathway by LH occurs at an unidentified site upstream of MAPK/ERK. Addiotional studies are needed to dissect the pathway by which LH signals to the MAPK/ERK cascade as well as to identify the functional significance of MAP/ERK activation to granulosa cells. In an effort to elucidate how activation of PKA leads to distinct FSSH- and LH- dependent responses, we have initiated studies on the A-kinase anchoring protein (AKAP) family of proteins and have identified unique regulation AKAPs in ovarian cells. AKAPs are very interesting proteins which not only dock PKA near its substrate but also appear to function as scaffolds for other signaling pathways, by binding a variety of signaling proteins including other protein kinases, phosphosphatases, and phosdiesterases. The functions of these AKAPs in ovarian granulosa cells and their requirement for signaling by both LH and FSH is currently under investigation.   REPRESENTATIVE PUBLICATIONS: Hunzicker-Dunn M, Maizels ET. (2006) FSH Signaling Pathways in Immature Granulosa Cells that Regulate Target Gene Expression: Branching out from Protein Kinase A. Cellular Signaling, in press. Hunzicker-Dunn M, Mayo K. (2006) Gonadotropin in signaling in the ovary. THe Physiology of Reproduction, 3rd Edition, Jimmy D. Neil, editor, Elsevier, Inc., San Diego, CA. Park Y, Maizels ET, Feiger ZJ, ALam H, Peters CA, Woodruff TK, Unterman TG, Lee Ej, Jameson JL, Hunzicker-Dunn M. (2005) Induction of cyclin D2 in rat granulosa cells requires FSH-dependent relief from FOXO1 repression coupled with positive signals from Smad. J Biol Chem. 280(10):9135-48. Salvador LM, Flynn MP, Avila J, Reierstad S, Maizels ET, ALam H, Park Y, Scott JD, Carr DW, Hunzicker-Dunn M. (2004) Neuronal microtubule-associated protein 2D is a dual a-kinase anchoring protein expressed in rat ovarian granulosa cells. J Biol Chem. 279(26):27621-32. Alam H, Maizels ET, Park Y, Ghaey S, Feiger ZJ, Chandel NS, Hunzicker-Dunn M. (2004) Follicle-stimulating hormone activation pf hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation. J Biol CHem 279(19):19431-40. Cottom J, Salvador LM, Maizels ET, Reierstad S, Park Y, Carr DW, Davare MA, Hell JW, Palmer SS< Dent P, Kawakatsu H, Ogata M, Hunzicker-Dunn M. (2003) Follicle stimulating hormone activates extracekkykar signal-regulated kinase but not extracellular signal -regulated kinase through a 100-kDa phosphotyrosine phosphatase. J Biol Chem. 278(9):7167-79. Salvador LM, Maizels E, Hales DB, Miyamoto E, Yammamoto H, Hunzicker-Dunn M. (2002) Acute signaling by the LH receptor is independent of protein kinase C activation, Endocrinologu. 143(8):2986-94. Hunziker-Dunn M, Gurevich VV, Casanova JE, Mukherjee S. (2002) ARF6: A newly appreciated player in G protein-coupled receptor desensitization. FEBS Lett. 521(1-3):3-8. Review. Duan WR, Ito M, Park Y, Maizels ET, Hunzicker-Dunn M, Jameson JL. (2002) Gonadotropin releasing hormone _GnRH_ regulates early growth response protein 1 (ERG-1) transcription through multiple promoter elements. Molecular ENdo 16, 221-33. Mukherjee S, Gurevich VV, Preninger A, Hamm H, Bader MF, Fazleabas A, Birnbaumer L, Hunzicker-Dunn M. (2002) Aspartiv acid 546 in the third cytoplasmic loop of luteinizing hormone/choriogonadotropin receptor is crucial for phosphorylation-independent interaction with arrestin2. J Biol Chem 277, 17916-27.