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DARPP-32 is required for MAPK/ERK signaling in thyroid cells


, : DARPP-32 is required for MAPK/ERK signaling in thyroid cells. Molecular Endocrinology 26(3): 471-480

Modulation of MAPK signaling duration by cAMP defines its physiological output by driving cells toward proliferation or differentiation. Understanding how the kinetics of MAPK signaling are integrated with other cellular signals is a key issue in development and cancer. Here we show that dopamine and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32), a protein required for thyroid cell differentiation, determines whether MAPK/ERK activation is sustained or transient. Serum, a stimulus that activates MAPK signaling and does not independently increase DARPP-32 levels results in transient activation of the MAPK pathway. By contrast, TSH + (IGF-I) activate MAPK signaling but also independently increase DARPP-32 levels. Our results are consistent with a model in which maintenance of DARPP-32 expression by TSH + IGF-I leads to sustained MAPK signaling. Moreover, the sensitivity of MAPK/ERK signaling in thyroid cells is lost when de novo DARPP-32 expression is blocked by small interfering RNA. Because both DARPP-32 levels and function as inhibitor of protein phosphatase 1, a key inhibitor of MAPK kinase activity, are governed by cAMP/protein kinase A, the results may explain why in thyroid cells cAMP signaling downstream from TSH controls the duration of MAPK pathway activity. Thus, fine-tuning of DARPP-32 levels leads to changes in the kinetics or sensitivity of MAPK/ERK signaling. Given the implications of MAPK signaling in thyroid cancer and the loss of DARPP-32 in tumor and transformed thyroid cells, DARPP-32 may represent a key therapeutic target.

US$19.90

PMID: 22301787

DOI: 10.1210/me.2011-1309


Other references

Willegger, M.; Kolb, A.; Chiari, C., 2017: Deformity in Skeletally Immature Patients - Diagnostic Procedures. Zeitschrift für Orthopadie und Unfallchirurgie 155(1): 105-119

Perry, R., 1982: Changing times for the guanaco. Country Life (London): 171: 420-422 No. 4409

Moser, R.; Spreng, P., 1970: The importance of tissue fixation in clinical practice. Das Medizinische Laboratorium 23(3): 60-69

Leocata P.; Discepoli S.; Calvisi G.; D.M.rco B.; Ventura T., 1987: Colorectal carcinoma correlation between cytohistological grading staging and prognosis study of 90 cases. The cytohistologic grading, the infiltration of parietal muscle, and the incidence of involvement of lymph nodes, from 90 patients with colorectal cancer, was analysed and compared with the survival to 6 months, 1, 2, 3 years after resection. Path...

Corradetti, A., 1935: Researches on Crosses between the Varieties of A. maculipennis. In continuation of research in Italy on races of Anopheles maculipennis, Mg. and in reference to the work of others, the author has attempted to discover the results of crosses between A. sacharovi, Favr (elutus, Edw.), which he here regards as a...

Pelikan V., 1979: Estimation of safe yield using the image pumping well method. Memoires Association Internationale des Hydrogeologues = Memoires International Association of Hydrogeologists: , Pages 37-39. 1979.

Kroeger, E.A.; Marshall, J.M., 1973: Beta-adrenergic effects on rat myometrium: mechanisms of membrane hyperpolarization. American Journal of Physiology 225(6): 1339-1345

Kalf F., 1988: Modelling in the Murray Basin: an overview. Record - Bureau of Mineral Resources, Geology and Geophysics Pages 93

Doyle Jones, P.S.; Sullins, K.E.; Saunders, G.K., 2002: Synovial regeneration in the equine carpus after arthroscopic mechanical or carbon dioxide laser synovectomy. Objective: To compare synovial regeneration in the equine carpus after mechanical or CO<sub>2</sub> laser synovectomy. Study Design: Arthroscopic partial synovectomy was performed in the radiocarpal and intercarpal joints. Sample Popul...

Tschuch, G., 1986: Acoustic communication in Gryllus bimaculatus (Orthoptera). A laboratory study using Gryllus bimaculatus showed that many female crickets sychronized their directed run to the source of the male calling song. Each part of the run had a constant velocity. Velocity increased in each successive part of the ru...