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Cellular and Developmental Biology of TRPM7 Channel-Kinase: Implicated Roles in Cancer.

Yee NS, Kazi AA, Yee RK - Cells (2014)

Bottom Line: Accumulating evidence indicates that TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration.Experimental studies in model organisms, such as zebrafish, mouse, and frog, have begun to elucidate the pleiotropic roles of TRPM7 during embryonic development from gastrulation to organogenesis.Studying the functional roles of TRPM7 and the underlying mechanisms in normal cells and developmental processes is expected to help understand how TRPM7 channel-kinase contributes to pathogenesis, such as malignant neoplasia.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine, Program of Experimental Therapeutics, Penn State Hershey Cancer Institute, Penn State Milton S, Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA. nyee@hmc.psu.edu.

ABSTRACT
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed cation-permeable ion channel with intrinsic kinase activity that plays important roles in various physiological functions. Biochemical and electrophysiological studies, in combination with molecular analyses of TRPM7, have generated insights into its functions as a cellular sensor and transducer of physicochemical stimuli. Accumulating evidence indicates that TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration. Experimental studies in model organisms, such as zebrafish, mouse, and frog, have begun to elucidate the pleiotropic roles of TRPM7 during embryonic development from gastrulation to organogenesis. Aberrant expression and/or activity of the TRPM7 channel-kinase have been implicated in human diseases including a variety of cancer. Studying the functional roles of TRPM7 and the underlying mechanisms in normal cells and developmental processes is expected to help understand how TRPM7 channel-kinase contributes to pathogenesis, such as malignant neoplasia. On the other hand, studies of TRPM7 in diseases, particularly cancer, will help shed new light in the normal functions of TRPM7 under physiological conditions. In this article, we will provide an updated review of the structural features and biological functions of TRPM7, present a summary of current knowledge of its roles in development and cancer, and discuss the potential of TRPM7 as a clinical biomarker and therapeutic target in malignant diseases.

No MeSH data available.


Related in: MedlinePlus

A schematic diagram to illustrate the protein structure of TRPM7 channel-kinase.
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cells-03-00751-f001: A schematic diagram to illustrate the protein structure of TRPM7 channel-kinase.

Mentions: The human TRPM7 gene is located on the long arm of chromosome 15, and it consists of 39 exons that span over 134.34 kb. There are nine splice variants of this gene and only four of the nine transcripts encode protein. The full-length transcript of TRPM7 contains 7263 nucleotides. The TRPM7 protein is composed of 1,865 amino acids with a molecular weight of 210 kDa. The basic structural features of the TRPM7 protein are homologous and to some extent, conserved among various members of the TRPM channels, as previously reviewed [15]. TRPM7 is similar to TRPM6 (with about 50% identity of protein) and, to a lesser extent, TRPM2, and these are the only known examples of “chanzymes”. Both TRPM7 and TRPM6 channels possess an atypical α-type serine/threonine protein kinase domain in the carboxyl terminus [15]. The channel pore forming segment, serine/threonine rich region, and kinase domain constitute the core components for the functions of TRPM7 (Figure 1). Moreover, the TRPM7 genes and the core functional domains of TRPM7 protein are highly conserved among various species of vertebrates including human, mouse, rat, and zebrafish (NCBI HomoloGene database).


Cellular and Developmental Biology of TRPM7 Channel-Kinase: Implicated Roles in Cancer.

Yee NS, Kazi AA, Yee RK - Cells (2014)

A schematic diagram to illustrate the protein structure of TRPM7 channel-kinase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4197629&req=5

cells-03-00751-f001: A schematic diagram to illustrate the protein structure of TRPM7 channel-kinase.
Mentions: The human TRPM7 gene is located on the long arm of chromosome 15, and it consists of 39 exons that span over 134.34 kb. There are nine splice variants of this gene and only four of the nine transcripts encode protein. The full-length transcript of TRPM7 contains 7263 nucleotides. The TRPM7 protein is composed of 1,865 amino acids with a molecular weight of 210 kDa. The basic structural features of the TRPM7 protein are homologous and to some extent, conserved among various members of the TRPM channels, as previously reviewed [15]. TRPM7 is similar to TRPM6 (with about 50% identity of protein) and, to a lesser extent, TRPM2, and these are the only known examples of “chanzymes”. Both TRPM7 and TRPM6 channels possess an atypical α-type serine/threonine protein kinase domain in the carboxyl terminus [15]. The channel pore forming segment, serine/threonine rich region, and kinase domain constitute the core components for the functions of TRPM7 (Figure 1). Moreover, the TRPM7 genes and the core functional domains of TRPM7 protein are highly conserved among various species of vertebrates including human, mouse, rat, and zebrafish (NCBI HomoloGene database).

Bottom Line: Accumulating evidence indicates that TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration.Experimental studies in model organisms, such as zebrafish, mouse, and frog, have begun to elucidate the pleiotropic roles of TRPM7 during embryonic development from gastrulation to organogenesis.Studying the functional roles of TRPM7 and the underlying mechanisms in normal cells and developmental processes is expected to help understand how TRPM7 channel-kinase contributes to pathogenesis, such as malignant neoplasia.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine, Program of Experimental Therapeutics, Penn State Hershey Cancer Institute, Penn State Milton S, Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA. nyee@hmc.psu.edu.

ABSTRACT
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed cation-permeable ion channel with intrinsic kinase activity that plays important roles in various physiological functions. Biochemical and electrophysiological studies, in combination with molecular analyses of TRPM7, have generated insights into its functions as a cellular sensor and transducer of physicochemical stimuli. Accumulating evidence indicates that TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration. Experimental studies in model organisms, such as zebrafish, mouse, and frog, have begun to elucidate the pleiotropic roles of TRPM7 during embryonic development from gastrulation to organogenesis. Aberrant expression and/or activity of the TRPM7 channel-kinase have been implicated in human diseases including a variety of cancer. Studying the functional roles of TRPM7 and the underlying mechanisms in normal cells and developmental processes is expected to help understand how TRPM7 channel-kinase contributes to pathogenesis, such as malignant neoplasia. On the other hand, studies of TRPM7 in diseases, particularly cancer, will help shed new light in the normal functions of TRPM7 under physiological conditions. In this article, we will provide an updated review of the structural features and biological functions of TRPM7, present a summary of current knowledge of its roles in development and cancer, and discuss the potential of TRPM7 as a clinical biomarker and therapeutic target in malignant diseases.

No MeSH data available.


Related in: MedlinePlus