MAPK8IP1
Description
The MAPK8IP1 (mitogen-activated protein kinase 8 interacting protein 1) is a protein-coding gene located on chromosome 11.
C-jun-amino-terminal kinase-interacting protein 1 is an enzyme that in humans is encoded by the MAPK8IP1 gene. The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions as a DNA-binding transactivator of the glucose transporter GLUT2. RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. This gene is found to be mutated in a type 2 diabetes family, and thus is thought to be a susceptibility gene for type 2 diabetes.
== Interactions == MAPK8IP1 has been shown to interact with MAP3K10, DUSP16, Mitogen-activated protein kinase 9, MAPK8, LRP2, LRP1, MAP3K12, MAP2K7, MAPK8IP2 and MAP3K11.
MAPK8IP1, also known as JIP1, is a scaffold protein that plays a crucial role in mediating JNK signaling. It assembles specific components of the MAPK cascade into a functional JNK signaling module, enabling JNK activation in response to excitotoxic stress. When localized in the cytoplasm, MAPK8IP1 inhibits JNK-regulated activity by retaining JNK in the cytoplasm and preventing JNK phosphorylation of c-Jun. MAPK8IP1 may also participate in ApoER2-specific reelin signaling. It directly or indirectly regulates GLUT2 gene expression and beta-cell function, suggesting a role in cell signaling in mature and developing nerve terminals. MAPK8IP1 might function as a regulator of vesicle transport, interacting with JNK-signaling components and motor proteins. It acts as an anti-apoptotic protein, influencing the survival of beta-cells. In conjunction with SH3RF1, MAPK8IP1 acts as a scaffold protein, organizing various components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1, and/or MAPK9/JNK2, into a functional multiprotein complex to ensure effective activation of the JNK signaling pathway. MAPK8IP1 regulates the activation of MAPK8/JNK1 and the differentiation of CD8(+) T-cells.
MAPK8IP1 is also known as IB1, JIP-1, JIP1, PRKM8IP.
