Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

G-protein signaling M-RAS regulation pathway


Log In to Post A Comment

G-protein signaling M-RAS regulation pathway

M-RAS regulation pathway

Muscle RAS oncogene homolog ( M-RAS ) is a novel member of Ras family of smallGTPases which mediates cell differentiation, survival and oncogenic transformation [1], [2], [3], [4].

Guanine nucleotide exchange factors (GEFs) are essential for M-RAS activationby promoting GTP loading on M-RAS. GTPase activating proteins (GAPs) negativelyregulates M-RAS activity by stimulating hydrolysis of GTP to GDP [5].

Main GEFs for M-RAS are: RAS guanyl releasing proteins 1 and 3 (CALDAG-GEFII and CALDAG-GEFIII ), Ras protein-specific guaninenucleotide-releasing factor 1 ( RASGRF1 ) and Son of sevenless homolog (SOS ) [6], [7], [5], [8].CALDAG-GEFII and CALDAG-GEFIII can be activated by increased Ca(2+)cytosol and DAG levels [7], [9], [5].RASGRF1 is activated by Lymphocyte-specific protein tyrosine kinase ( Lck )phosphorylation [6], [7], [10].

Known GAP for M-RAS is RAS p21 protein activator 1 ( p120GAP ) [7]. Breakpoint cluster region ( BCR ) via Docking protein 1 and 2 (DOK1 and DOK2 ) phosphorylation stimulates GAP activity of p120GAP[11], [5]. Binding of RAP1A member of RAS oncogene family (RAP-1A ) and V-src sarcoma ( c-Src ) phosphorylation suppress GAP activityof p120GAP [12], [10]. RAS p21 protein activator 2 (RASA2 ) also exhibits GAP activity towards M-RAS. RASA2 isactivated by Inositol 1,3,4,5-tetrakisphosphate binding or G-protein alpha-12family signaling [7]. Another known M-RAS GAP is Neurofibromin 1( Neurofibromin ) [7].

GTP-bound M-RAS can stimulate the Raf kinase family members v-raf-1 murineleukemia viral oncogene homolog 1 ( c-Raf-1), v-raf murine sarcoma viral oncogenehomolog B1 (B-Raf) and v-raf murine sarcoma 3611 viral oncogene homolog (A-Raf-1 ) and thus promote Mitogen-activated protein kinases 1, 3 ( ERK1/2) activation [3], [13].