TCL (GTPase)

Last updated

TCL is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rho family of GTPases.,. [1] [2]

TCL (TC10-like) shares 85% and 78% amino acid similarity to TC10 and Cdc42, respectively. TCL mRNA is 2.5 kb long and is mainly expressed in heart. In vitro, TCL shows rapid GDP/GTP exchange and displays higher GTP dissociation and hydrolysis rates than TC10. Like other Rac/Cdc42/RhoUV members, GTP-bound TCL interacts with CRIB domains, such as those found in PAK and WASP. TCL produces large and dynamic F-actin-rich ruffles on the dorsal cell membrane in REF-52 fibroblasts. TCL activity is blocked by dominant negative Rac1 and Cdc42 mutants, suggesting a cross-talk between these three Rho GTPases. [3]

TCL is unrelated to TCL1A, a proto-oncogene implicated in the development of T-Cell Leukemias.

See also

Related Research Articles

The lamellipodium is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional actin mesh; the whole structure propels the cell across a substrate. Within the lamellipodia are ribs of actin called microspikes, which, when they spread beyond the lamellipodium frontier, are called filopodia. The lamellipodium is born of actin nucleation in the plasma membrane of the cell and is the primary area of actin incorporation or microfilament formation of the cell.

Guanine nucleotide exchange factor Proteins which remove GDP from GTPases

Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.

The Rho family of GTPases is a family of small signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions.

CDC42 Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog, also known as Cdc42, is a protein involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

FGD1

FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. Orthologs of the FGD1 gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and C. elegans. It is a member of the FYVE, RhoGEF and PH domain containing family.

RAC1

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

Transforming protein RhoA Protein-coding gene in the species Homo sapiens

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

IQGAP1

Ras GTPase-activating-like protein IQGAP1 (IQGAP1) also known as p195 is a ubiquitously expressed protein that in humans is encoded by the IQGAP1 gene. IQGAP1 is a scaffold protein involved in regulating various cellular processes ranging from organization of the actin cytoskeleton, transcription, and cellular adhesion to regulating the cell cycle.

RAC2

Rac2 is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2.

ARHGDIA

Rho GDP-dissociation inhibitor 1 is a protein that in humans is encoded by the ARHGDIA gene.

RHOQ

Rho-related GTP-binding protein RhoQ is a protein that in humans is encoded by the RHOQ gene.

RhoG

RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.

RhoD

RhoD is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOD.

Rnd2

Rnd2 is a small signaling G protein, and is a member of the Rnd subgroup of the Rho family of GTPases. It is encoded by the gene RND2.

RhoV is a small signaling G protein, and is a member of the Rho family of GTPases. Chp was identified in 1998 as a GTPase interacting with the p21 activated kinase PAK2. RhoV/Chp delineates with RhoU/Wrch a Rho subclass related to Rac and Cdc42, which emerged in early multicellular organisms during evolution. RhoV/Chp depends on palmitoylation rather than prenylation for association with plasma and intracellular membranes. In Xenopus embryos, RhoV is encoded by a canonical Wnt response gene and is induced in the developing neural crest at specification. RhoV activity cooperates with the Snai1 (Snail) transcription factor for the subsequent induction of the pro-invasive transcription factors Snai2 (Slug), Sox9 or Twist.

Rac is a subfamily of the Rho family of GTPases, small signaling G proteins. When bound to GTP, Rac is activated. In its activated state, Rac participates in the regulation of cell movement, through its involvement in structural changes to the actin Cytoskeleton.

RhoU is a small signaling G protein, and is a member of the Rho family of GTPases. Wrch1 was identified in 2001 as encoded by a non-canonical Wnt induced gene. RhoU/Wrch delineates with RhoV/Chp a Rho subclass related to Rac and Cdc42, which emerged in early multicellular organisms during evolution.

CDC42EP4

Cdc42 effector protein 4 is a protein that in humans is encoded by the CDC42EP4 gene.

RHOJ

Rho-related GTP-binding protein RhoJ is a protein that in humans is encoded by the RHOJ gene.

PLEKHG2

Pleckstrin homology domain containing, family G member 2 (PLEKHG2) is a protein that in humans is encoded by the PLEKHG2 gene. It is sometimes written as ARHGEF42, FLJ00018.

References

  1. Ridley A. (2006). "Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking". Trends Cell Biol. 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. PMID   16949823.
  2. Boureux A, Vignal E, Faure S, Fort P (2007). "Evolution of the Rho family of ras-like GTPases in eukaryotes". Mol Biol Evol. 24 (1): 203–16. doi:10.1093/molbev/msl145. ISSN   0021-9193. PMC   2665304 . PMID   17035353.
  3. Vignal E, De Toledo M, Comunale F, Ladopoulou A, Gauthier-Rouviere C, Blangy A, Fort P (2007). "Characterization of TCL, a new GTPase of the rho family related to TC10 and Ccdc42". J Biol Chem. 275 (46): 36457–64. doi: 10.1074/jbc.M003487200 . ISSN   0021-9258. PMID   10967094.