Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

hGrb10alpha (previously named Grb-IR) is a Src-homology 2 domain-containing protein that binds with high affinity to the tyrosine-phosphorylated insulin receptor and insulin-like growth factor-1 receptor. At least two isoforms of human Grb10, (hGrb10alpha and hGrb10beta), which differ in the pleckstrin homology (PH) domain and the N-terminal sequence, have previously been identified in insulin target tissues such as human skeletal muscle and fat cells. Here we report the cloning of the third isoform of the hGrb10 family (hGrb10gamma) from human skeletal muscle and its localization to human chromosome 7. We have also determined the human chromosome localization of Grb7 to 17q21-q22 and Grb14 to chromosome 2. hGrb10gamma contains an intact PH domain and an N-terminal sequence that is present in hGrb10alpha but absent in hGrb10beta. RNase protection assays and Western blot analysis showed that hGrb10alpha and hGrb10gamma are differentially expressed in insulin target cells including skeletal muscle, liver, and adipocyte cells. hGrb10gamma is also expressed in HeLa cells and various breast cancer cell lines. The protein bound with high affinity to the insulin receptor in cells, and the interaction was dependent on the tyrosine phosphorylation of the receptor. hGrb10gamma also underwent insulin-stimulated membrane translocation and serine phosphorylation. hGrb10gamma phosphorylation was inhibited by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, and wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase. Taken together, our data suggest that hGrb10 isoforms are potential downstream signaling components of the insulin receptor tyrosine kinase and that the PH domain may play an important role in the involvement of these isoforms in signal transduction pathways initiated by insulin and other growth factors.
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PMID:Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma. 936 Sep 86

Megakaryocyte differentiation is often accompanied by the changes of gene expression pattern. Here we reported that the expression of DAB2, a putative adaptor protein in cell signaling, was induced at the protein and mRNA levels upon 12-O-tetradecanoylphorbol-13-acetate-mediated megakaryocyte differentiation of human chronic myeloid leukemic K562 cells. On the other hand, the differentiation agents DMSO and retinoic acid had no effect on DAB2 expression. Analysis of promoter activity with the human DAB2 luciferase reporter constructs suggested that the regulation is partially at the transcriptional level. The responsive sequences located within an 80-bp DAB2 promoter region. To determine the involvement of MEK1-p42/p44 MAPK pathway in mediating DAB2 gene expression, we have performed the following experiments and found that (i) there was sustained activation of p42/p44 MAPK, but not p38 MAPK, upon K562 cells differentiation; (ii) application of MEK1 inhibitor U0126 reduced the expression of DAB2 protein, mRNA and promoter activity, as well as cell differentiation; (iii) constitutively active MEK1 increased DAB2 promoter activity; and (iv) dominant negative ERK2 abolished constitutively active MEK1-induced DAB2 promoter activity. Taken together, our results indicate that DAB2 gene is induced upon megakaryocyte differentiation by the MEK1-p42/p44 MAPK pathway and may define a new role of DAB2 in hematopoietic cell differentiation.
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PMID:Induction of disabled-2 gene during megakaryocyte differentiation of k562 cells. 1143 82