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Literature summary for 3.6.5.2 extracted from

  • Kumar, S.; Xu, J.; Kumar, R.S.; Lakshmikanthan, S.; Kapur, R.; Kofron, M.; Chrzanowska-Wodnicka, M.; Filippi, M.D.
    The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation (2014), J. Exp. Med., 211, 1741-1758.
    View publication on PubMedView publication on EuropePMC
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Mus musculus
-
 GDP + phosphate
-
 ?
GTP + H2O Mus musculus C57BL/6
-
 GDP + phosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus Q99JI6 gene Rap1b
-
Mus musculus C57BL/6 Q99JI6 gene Rap1b
-

Source Tissue

Source Tissue Comment Organism Textmining
endothelial cell
-
 Mus musculus
-
hematopoietic cell
-
 Mus musculus
-
lung
-
 Mus musculus
-
additional information Rap1b is expressed in all tissues, including endothelial cells Mus musculus
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neutrophil Rap1b is the predominant Rap1 isoform expressed in neutrophils Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
 Mus musculus GDP + phosphate
-
 ?
GTP + H2O
-
 Mus musculus C57BL/6 GDP + phosphate
-
 ?

Synonyms

Synonyms Comment Organism
Rap1b
-
 Mus musculus
Ras proximity 1
-
 Mus musculus
small GTPase
-
 Mus musculus

General Information

General Information Comment Organism
evolution Ras proximity 1 (Rap1) belongs to the Ras superfamily of GTPases that cycle between GTP-bound active and GDPbound inactive forms through GEFs and GAPs Mus musculus
malfunction Rap1b deficiency increases neutrophil transmigration, Rap1b loss promotes transendothelial migration via transcellular route. Rap1b-deficient mice exhibits enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. Rap1b-/- neutrophils exhibit enhanced chemokinesis and chemotaxis. Rap1b deficiency promotes the transcellular route of diapedesis through endothelial cell. Increased transcellular migration of Rap1b-deficient neutrophils in vitro is selectively mediated by enhanced PI3K-Akt activation and invadopodia-like protrusions. Akt inhibition in vivo suppresses excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. Pharmacological inhibition of Akt activation rescued Rap1b-/- neutrophil phenotype. Rap1a expression does not compensate for Rap1b loss in blood cells. Phenotype, overview Mus musculus
physiological function the small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. The inhibitory action of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Role for Rap1b as a key suppressor of neutrophil migration and lung inflammation, which may represent an unappreciated regulatory pathway of neutrophil-related aberrant inflammatory responses. Rap1b inhibits Akt activation via CD11b outside-in signaling, Rap1b negatively regulates PI3K-Akt signaling via the phosphatase SHP-1 Mus musculus