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The AKT Pathway is Involved in the Proliferation of CAD Cells and is Perturbed by MC3R
Author(s) -
Wachira James M,
Temoney Shonanate,
Mekuria Tassew,
HughesDarden Cleo
Publication year - 2007
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.21.6.lb17-c
Subject(s) - protein kinase b , microbiology and biotechnology , biology , signal transduction , g protein coupled receptor , endosome , cell growth , biochemistry , intracellular
The melanocortin system shows a high degree of evolutional conservation and it is critically involved in many facets of homeostasis. Although it is well established that melanocortin receptors function by activating membrane bound adenylate cyclase, MC3R and some other G protein coupled receptors (GPCRs) are known to activate cell‐growth signaling pathways consequent to their endocytosis. We hypothesized that in addition to the primary cAMP response, MC3R impinges on other signaling pathways in neuronal cells. Luciferase reporter gene assays showed the constitutive activation of cyclic AMP response element (CRE) in CAD cells ectopically expressing MC3R which could be further enhanced by treatment with gamma‐2‐MSH. Recruitment of arrestins is implicated in the activation of secondary pathways by GPCRs and our data showed the colocalization of MC3R with arrestin B2 in endosomes. Induction of differentiation to neurons with insulin, selenium and transferrin mixture led to an increased and sustained activation of protein kinase B (PKB) in both vector control and MC3R transfectants. An alteration in the distribution of PKB species was observed in MC3R transfectants. Nonetheless, inhibition of PKB pathway with triciribine abrogated cell proliferation in both vector control and MC3R transfectants. These studies suggest that the AKT/PKB pathway plays an important role in the maintenance of a transformed state in CAD cells and hint to a link between MC3R and cell growth pathways that may involve the dephosphorylation of AKT. This work is supported by MBRS‐SCORE grant #2SO6‐GM051971 and RCMI grant # G12RR017581.