Tribbles Homolog 1 (TRIB1)

TRIB1 is likely to be inactive, since it lacks the active-site lysine within the serine/threonine kinase-like domain. Quantitative real-time PCR of several tissues detected highest TRIB1 expression in skeletal muscle, thyroid, pancreas, peripheral blood leukocytes, and bone marrow.Overexpression of TRIB1 inhibited oncogenic Ras (HRAS)-driven AP1 activation and MEKK1 (MAP3K1)-mediated AP1 activation. ERK activation was enhanced by TRIB1. Coimmunoprecipitation and yeast 2-hybrid assays showed that MEK1 (MAP2K1) interacted with both TRIB1 and TRIB3, and MKK4 (MAP2K4) interacted specifically with TRIB1. Cotransfection of MKK4 enhanced the level of TRIB1, indicating that the TRIB-MAPKK interaction stabilized TRIB1.