| |
| |
Gene Symbol |
MAP3K4 |
| |
Aliases |
MAPKKK4, MEKK 4, MEKK4, MTK1, PRO0412 |
| |
Entrez Gene ID |
|
| |
Gene Name |
Mitogen-activated protein kinase kinase kinase 4 |
| |
Chromosomal Location |
6q26 |
| |
HGNC ID |
|
| |
Summary |
The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]
|
| |
e!Ensembl
|
| Protein Information |
| |
Protein Name |
Mitogen-activated protein kinase kinase kinase 4, MAP three kinase 1, MAP/ERK kinase kinase 4, MAPK/ERK kinase kinase 4, MEK kinase 4, SSK2/SSK22 MAP kinase kinase kinase, yeast, homolog of, dJ473J16.1 (mitogen-activated protein kinase kinase kinase 4), predicted protein of HQ0412 |
| |
Function |
|
Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. |
|
| |
UniProt |
|
| |
Pfam |
| Pfam Accession |
Pfam ID |
| PF00069 |
Pkinase |
|
|
|
|
|
|
Interactions |
| | |
| STRING |
MINT |
IntAct |
| ENSP00000216181 |
P35579 |
P35579 |
|
| | |
View interactions
|
| |
| |
Associated Diseases
| Disease group | Disease Name | References |
| Endocrine System Diseases |
| PCOS |
|
| Neoplasms |
| Bilateral Wilms Tumor |
|
| Nephroblastoma |
|
| Endometrial Cancer |
|
| Reproductive disorders |
| Endometriosis |
|
|
|
References |
| |
| |
| Lan Chen-Wei, Chen Mei-Jou, Tai Kang-Yu, Yu Danny Cw, Yang Yu-Chieh, Jan Pey-Shynan, Yang Yu-Shih, Chen Hsin-Fu, Ho Hong-Nerng |
| Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Genome and Systems Biology Degree Program, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan university Taipei, Taiwan.| Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.| Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.| Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan university Taipei, Taiwan. |
| Sci Rep. 2015 Oct 13;5:14994. doi: 10.1038/srep14994. |
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Although its aetiology and pathogenesis remain unclear, recent studies suggest that the dysfunction of granulosa cells may partly be responsible. This study aimed to use cDNA microarray technology to compare granulosa cell gene expression profiles in women with and without PCOS to identify genes that may be aetiologically implicated in the pathogenesis of PCOS. The study cohort included 12 women undergoing in vitro fertilization, six with PCOS and six without PCOS. Differential gene expression profiles were classified by post-analyses of microarray data, followed by western blot analyses to confirm the microarray data of selected genes. In total, 243 genes were differentially expressed (125 upregulated and 118 downregulated) between the PCOS and non-PCOS granulosa cells. These genes are involved in reproductive system development, amino acid metabolism and cellular development and proliferation. Comparative analysis revealed genes involved in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) signaling pathways. Western blot analyses confirmed that mitogen-activated protein kinase kinase kinase 4 and phospho-ERK1/2 were decreased in PCOS granulosa cells. This study identified candidate genes involved in MAPK/ERK signaling pathways that may influence the function of granulosa cells in PCOS. |
|
|
|
| |
| © 2019, Biomedical Informatics Centre, NIRRH |
National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai-400 012
Tel: 91-22-24192104, Fax No: 91-22-24139412
|
