Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycoprotein hormones, ACTH, TSH, FSH, and LH regulate diverse functions in endocrine cells. Although cAMP and PKA have long been shown to mediate specific intracellular signaling events including the transcription of specific genes via the CREB-CBP complex, recent observations have indicated that PKA does not account for all of the intracellular targets of cAMP. For example, TSH stimulation of thyroid cell proliferation is not completely blocked by PKA inhibitors. TSH and FSH can stimulate PKB phosphorylation by a PKAindependent but PI3-K/PDK1-dependent pathway. An FSH inducible kinase, Sgk, has recently been shown to be a close relative of PKB. Sgk is also a target of PI3-K-PDK1 pathway, indicating that some effects previously ascribed to PKB may be mediated by this inducible kinase. The identification of novel cAMP-binding proteins that exhibit guanine nucleotide exchange (GEF) activity (cAMP-GEFS; Epacs) has open new doors for cAMP action that include activation of small GTPases such as Rap1a, Rap2, and possibly Ras. These GTPases are known activators of downstream kinase cascades, including p38MAPK and Erk1/2 as well as PI3-K. Thus, FSH and TSH activation of PKB and Sgk may occur via this alternative cAMP pathway that involves cAMP-GEFs and the activation of the PI3-K/PDK1 pathway.
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PMID:New signaling pathways for hormones and cyclic adenosine 3',5'-monophosphate action in endocrine cells. 1115 28

Postnatal growth of the mouse adrenal gland shows a characteristic gender-dependent pattern, resulting in an almost 2-fold higher adrenal weight in 11-wk-old female vs. male mice. We demonstrated that the higher weight of the adrenal glands in female mice is due to a significantly (P < 0.05) increased growth rate in female mice and a shorter growth phase of the adrenal glands in male mice (P < 0.05). To address the signaling mechanisms underlying these differential growth patterns, we evaluated the phosphorylation levels of p44/42 and p38 MAPK. In female mice, age-dependent reductions of p38 MAPK phosphorylation were found between wk 3 and 9 (47% reduction; P < 0.05). At the age of 11 wk, the p38 MAPK phosphorylation level in female adrenal glands was about 60% lower than in the male counterparts (P < 0.01). Similarly, the phosphorylation level of p44/42 MAPK was 50% lower in female adrenal glands (P < 0.001). Reduced activation of p44/42 MAPK was also observed after growth stimulation of the adrenal glands in male mice after ACTH treatment (-36%; P < 0.001) or by expression of a GH transgene (-34%; P < 0.001), whereas p38 MAPK, JNK, or PDK1 activation was unaffected. From our findings in three independent mouse models where partial deactivation of p44/42 MAPK was observed under conditions of elevated growth, we suggest a function of p44/42 MAPK for adrenal growth and a role of p44/42 MAPK for the integration of different endocrine stimuli.
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PMID:Decreased p44/42 mitogen-activated protein kinase phosphorylation in gender- or hormone-related but not during age-related adrenal gland growth in mice. 1894 1