G-protein signaling - Rap2B regulation pathway

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Rap2B regulation pathway

RAP2B member of RAS oncogene family (Rap-2B) is a member of the Ras-like small GTPases family expressed in platelets. The protein is known to influence platelet activation [1], [2], [3].

Rap-2B is posttranslationally modified by geranylgeranylation, catalyzed by Geranylgeranyltransferase type I (GGTase-I) [4], [5].

Activity of Rap-2B is mainly regulated by guanine nucleotide exchange factors (GEFs) that promote GTP-bound (active) state of Rap-2B. Main GEFs for Rap-2B are Rap guanine nucleotide exchange factors 2 and 5 (PDZ-GEF1 and MR-GEF) [6]. Activated Adrenergic beta-1 receptor (Beta-1 adrenergic receptor) directly binds to PDZ-GEF1 and stimulates its GEF activity [7]. MR-GEF is regulated by Muscle RAS oncogene homolog (M-RAS) that binds to and inhibits MR-GEF activity [6].

Activated Rap-2B can stimulate enzymatic activity of Phospholipase C epsilon 1 (PLC-epsilon) [8], [9].

References:

  1. Ohmstede CA, Farrell FX, Reep BR, Clemetson KJ, Lapetina EG
    RAP2B: a RAS-related GTP-binding protein from platelets. Proceedings of the National Academy of Sciences of the United States of America 1990 Sep;87(17):6527-31
  2. Greco F, Sinigaglia F, Balduini C, Torti M
    Activation of the small GTPase Rap2B in agonist-stimulated human platelets. Journal of thrombosis and haemostasis : JTH 2004 Dec;2(12):2223-30
  3. Greco F, Ciana A, Pietra D, Balduini C, Minetti G, Torti M
    Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation. Biochimica et biophysica acta 2006 Mar;1763(3):330-5
  4. Bokoch GM
    Biology of the Rap proteins, members of the ras superfamily of GTP-binding proteins. The Biochemical journal 1993 Jan 1;289 ( Pt 1):17-24
  5. Farrell FX, Yamamoto K, Lapetina EG
    Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated. The Biochemical journal 1993 Jan 15;289 ( Pt 2):349-55
  6. Rebhun JF, Castro AF, Quilliam LA
    Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. The Journal of biological chemistry 2000 Nov 10;275(45):34901-8
  7. Pak Y, Pham N, Rotin D
    Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation. Molecular and cellular biology 2002 Nov;22(22):7942-52
  8. Wing MR, Bourdon DM, Harden TK
    PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling. Molecular interventions 2003 Aug;3(5):273-80
  9. Stope MB, Vom Dorp F, Szatkowski D, Bohm A, Keiper M, Nolte J, Oude Weernink PA, Rosskopf D, Evellin S, Jakobs KH, Schmidt M
    Rap2B-dependent stimulation of phospholipase C-epsilon by epidermal growth factor receptor mediated by c-Src phosphorylation of RasGRP3. Molecular and cellular biology 2004 Jun;24(11):4664-76

  1. Ohmstede CA, Farrell FX, Reep BR, Clemetson KJ, Lapetina EG
    RAP2B: a RAS-related GTP-binding protein from platelets. Proceedings of the National Academy of Sciences of the United States of America 1990 Sep;87(17):6527-31
  2. Greco F, Sinigaglia F, Balduini C, Torti M
    Activation of the small GTPase Rap2B in agonist-stimulated human platelets. Journal of thrombosis and haemostasis : JTH 2004 Dec;2(12):2223-30
  3. Greco F, Ciana A, Pietra D, Balduini C, Minetti G, Torti M
    Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation. Biochimica et biophysica acta 2006 Mar;1763(3):330-5
  4. Bokoch GM
    Biology of the Rap proteins, members of the ras superfamily of GTP-binding proteins. The Biochemical journal 1993 Jan 1;289 ( Pt 1):17-24
  5. Farrell FX, Yamamoto K, Lapetina EG
    Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated. The Biochemical journal 1993 Jan 15;289 ( Pt 2):349-55
  6. Rebhun JF, Castro AF, Quilliam LA
    Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. The Journal of biological chemistry 2000 Nov 10;275(45):34901-8
  7. Pak Y, Pham N, Rotin D
    Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation. Molecular and cellular biology 2002 Nov;22(22):7942-52
  8. Wing MR, Bourdon DM, Harden TK
    PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling. Molecular interventions 2003 Aug;3(5):273-80
  9. Stope MB, Vom Dorp F, Szatkowski D, Bohm A, Keiper M, Nolte J, Oude Weernink PA, Rosskopf D, Evellin S, Jakobs KH, Schmidt M
    Rap2B-dependent stimulation of phospholipase C-epsilon by epidermal growth factor receptor mediated by c-Src phosphorylation of RasGRP3. Molecular and cellular biology 2004 Jun;24(11):4664-76

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