KEGG   PATHWAY: rno04611
Entry
rno04611                    Pathway                                
Name
Platelet activation - Rattus norvegicus (rat)
Description
Platelets play a key and beneficial role for primary hemostasis on the disruption of the integrity of vessel wall. Platelet adhesion and activation at sites of vascular wall injury is initiated by adhesion to adhesive macromolecules, such as collagen and von Willebrand factor (vWF), or by soluble platelet agonists, such as ADP, thrombin, and thromboxane A2. Different receptors are stimulated by various agonists, almost converging in increasing intracellular Ca2+ concentration that stimulate platelet shape change and granule secretion and ultimately induce the "inside-out" signaling process leading to activation of the ligand-binding function of integrin alpha IIb beta 3. Binding of alpha IIb beta 3 to its ligands, mainly fibrinogen, mediates platelet adhesion and aggregation and triggers "outside-in" signaling, resulting in platelet spreading, additional granule secretion, stabilization of platelet adhesion and aggregation, and clot retraction.
Class
Organismal Systems; Immune system
Pathway map
rno04611  Platelet activation
rno04611

Other DBs
GO: 0030168
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
24816  Tbxa2r; thromboxane A2 receptor [KO:K04264]
29251  F2; prothrombin precursor [KO:K01313] [EC:3.4.21.5]
25439  F2r; proteinase-activated receptor 1 precursor [KO:K03914]
116498  F2rl3; proteinase-activated receptor 4 [KO:K04236]
303634  Gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
60323  Arhgef1; rho guanine nucleotide exchange factor 1 [KO:K12330]
367072  Arhgef12; rho guanine nucleotide exchange factor 12 [KO:K07532]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
81762  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
25537  Rock2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
24668  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
24669  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform 1 [KO:K06269] [EC:3.1.3.16]
25594  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
116670  Ppp1r12a; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
501203  Myl12a; myosin regulatory light chain RLC-A [KO:K12757]
50685  Myl12b; myosin regulatory light chain 12B [KO:K12757]
25505  P2rx1; P2X purinoceptor 1 isoform 1 [KO:K05215]
304496  Orai1; calcium release-activated calcium channel protein 1 [KO:K16056]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
361618  Stim1; stromal interaction molecule 1 precursor [KO:K16059]
288057  Mylk; myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
117558  Mylk2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
291926  Mylk3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
100911165  Mylk4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
25265  P2ry1; P2Y purinoceptor 1 [KO:K04270]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25522  Prkcz; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
84006  Prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
29434  Rasgrp1; RAS guanyl-releasing protein 1 [KO:K04350]
361714  Rasgrp2; RAS guanyl-releasing protein 2 [KO:K12361]
295347  Rap1a; ras-related protein Rap-1A [KO:K04353]
171337  Rap1b; ras-related protein Rap-1b precursor [KO:K07836]
307171  Apbb1ip; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
315776  Tln2; talin-2 [KO:K06271]
313494  Tln1; talin-1 [KO:K06271]
685269  Itga2b; integrin alpha-IIb precursor [KO:K06476]
29302  Itgb3; integrin beta-3 precursor [KO:K06493]
309186  Fermt3; fermitin family homolog 3 [KO:K17084]
361969  Fga; fibrinogen alpha chain isoform 1 precursor [KO:K03903]
24366  Fgb; fibrinogen beta chain precursor [KO:K03904]
24367  Fgg; fibrinogen gamma chain precursor [KO:K03905]
64803  P2ry12; P2Y purinoceptor 12 [KO:K04298]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
292661  Ptgir; prostacyclin receptor [KO:K04263]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
298947  Pik3cg; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
497931  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
497932  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
361517  Vasp; vasodilator-stimulated phosphoprotein [KO:K06274]
100361457  Actg1l1; actin, gamma 1 propeptide-like [KO:K05692]
81822  Actb; actin, cytoplasmic 1 [KO:K05692]
287876  Actg1; actin, cytoplasmic 2 [KO:K05692]
120098222  POTE ankyrin domain family member F [KO:K05692]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
306400  Arhgap35; rho GTPase-activating protein 35 [KO:K05732]
498276  Fcgr2al1; Fc gamma receptor 2A like 1 [KO:K06472]
134481532  low affinity immunoglobulin gamma Fc region receptor III isoform X1 [KO:K06472]
25155  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
84352  Col1a2; collagen alpha-2(I) chain precursor [KO:K06236]
29393  Col1a1; collagen alpha-1(I) chain precursor [KO:K06236]
84032  Col3a1; collagen alpha-1(III) chain precursor [KO:K19720]
684555  Gp6; platelet glycoprotein VI isoform X1 [KO:K06264]
25441  Fcer1g; high affinity immunoglobulin epsilon receptor subunit gamma precursor [KO:K07983]
81515  Lyn; tyrosine-protein kinase Lyn isoform A [KO:K05854] [EC:2.7.10.2]
25150  Fyn; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
170921  Itga2; integrin alpha-2 precursor [KO:K06481]
24511  Itgb1; integrin beta-1 precursor [KO:K05719]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
155918  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
367901  Btk; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
116669  Vwf; von Willebrand factor precursor [KO:K03900]
25259  Gp5; platelet glycoprotein V precursor [KO:K06260]
691992  Gp1ba; platelet glycoprotein Ib alpha chain precursor [KO:K06261]
116727  Gp1bb; platelet glycoprotein Ib beta chain precursor [KO:K06262]
502858  Gp9; platelet glycoprotein IX precursor [KO:K06263]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24600  Nos3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
66012  Gucy1a2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
497757  Gucy1a1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
25206  Gucy1b2; guanylate cyclase soluble subunit beta-2 isoform 2 [KO:K12319] [EC:4.6.1.2]
25202  Gucy1b1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
54286  Prkg1; cGMP-dependent protein kinase 1 [KO:K07376] [EC:2.7.11.12]
25523  Prkg2; cGMP-dependent protein kinase 2 [KO:K19477] [EC:2.7.11.12]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
691810  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
24693  Ptgs1; prostaglandin G/H synthase 1 precursor [KO:K00509] [EC:1.14.99.1]
24886  Tbxas1; thromboxane-A synthase [KO:K01832] [EC:5.3.99.5]
64630  Snap23; synaptosomal-associated protein 23 [KO:K08508]
83730  Vamp8; vesicle-associated membrane protein 8 [KO:K08512]
Compound
C00002  ATP
C00008  ADP
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00427  Prostaglandin H2
C00533  Nitric oxide
C00575  3',5'-Cyclic AMP
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01312  Prostaglandin I2
C02198  Thromboxane A2
C05956  Prostaglandin G2
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:21071698
  Authors
Li Z, Delaney MK, O'Brien KA, Du X
  Title
Signaling during platelet adhesion and activation.
  Journal
Arterioscler Thromb Vasc Biol 30:2341-9 (2010)
DOI:10.1161/ATVBAHA.110.207522
Reference
PMID:22119499
  Authors
Broos K, De Meyer SF, Feys HB, Vanhoorelbeke K, Deckmyn H
  Title
Blood platelet biochemistry.
  Journal
Thromb Res 129:245-9 (2012)
DOI:10.1016/j.thromres.2011.11.002
Reference
PMID:16149014
  Authors
Jurk K, Kehrel BE
  Title
Platelets: physiology and biochemistry.
  Journal
Semin Thromb Hemost 31:381-92 (2005)
DOI:10.1055/s-2005-916671
Reference
PMID:17158345
  Authors
Offermanns S
  Title
Activation of platelet function through G protein-coupled receptors.
  Journal
Circ Res 99:1293-304 (2006)
DOI:10.1161/01.RES.0000251742.71301.16
Reference
PMID:18174460
  Authors
Varga-Szabo D, Pleines I, Nieswandt B
  Title
Cell adhesion mechanisms in platelets.
  Journal
Arterioscler Thromb Vasc Biol 28:403-12 (2008)
DOI:10.1161/ATVBAHA.107.150474
Reference
PMID:18550847
  Authors
Yin H, Liu J, Li Z, Berndt MC, Lowell CA, Du X
  Title
Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway.
  Journal
Blood 112:1139-46 (2008)
DOI:10.1182/blood-2008-02-140970
Reference
PMID:19630797
  Authors
Bergmeier W, Stefanini L
  Title
Novel molecules in calcium signaling in platelets.
  Journal
J Thromb Haemost 7 Suppl 1:187-90 (2009)
DOI:10.1111/j.1538-7836.2009.03379.x
Reference
PMID:18544684
  Authors
Cifuni SM, Wagner DD, Bergmeier W
  Title
CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets.
  Journal
Blood 112:1696-703 (2008)
DOI:10.1182/blood-2008-02-139733
Reference
PMID:23106920
  Authors
Heemskerk JW, Mattheij NJ, Cosemans JM
  Title
Platelet-based coagulation: different populations, different functions.
  Journal
J Thromb Haemost 11:2-16 (2013)
DOI:10.1111/jth.12045
Reference
PMID:19286885
  Authors
Rivera J, Lozano ML, Navarro-Nunez L, Vicente V
  Title
Platelet receptors and signaling in the dynamics of thrombus formation.
  Journal
Haematologica 94:700-11 (2009)
DOI:10.3324/haematol.2008.003178
Reference
PMID:18363565
  Authors
Banno A, Ginsberg MH
  Title
Integrin activation.
  Journal
Biochem Soc Trans 36:229-34 (2008)
DOI:10.1042/BST0360229
Reference
PMID:20089227
  Authors
Angiolillo DJ, Ferreiro JL
  Title
Platelet adenosine diphosphate P2Y12 receptor antagonism: benefits and limitations of current treatment strategies and future directions.
  Journal
Rev Esp Cardiol 63:60-76 (2010)
DOI:10.1016/s1885-5857(10)70010-4
Reference
PMID:22701130
  Authors
Joo SJ
  Title
Mechanisms of Platelet Activation and Integrin alphaIIbeta3.
  Journal
Korean Circ J 42:295-301 (2012)
DOI:10.4070/kcj.2012.42.5.295
Reference
PMID:20002545
  Authors
Harper MT, Poole AW
  Title
Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation.
  Journal
J Thromb Haemost 8:454-62 (2010)
DOI:10.1111/j.1538-7836.2009.03722.x
Reference
PMID:23805129
  Authors
Fitch-Tewfik JL, Flaumenhaft R
  Title
Platelet granule exocytosis: a comparison with chromaffin cells.
  Journal
Front Endocrinol (Lausanne) 4:77 (2013)
DOI:10.3389/fendo.2013.00077
Reference
PMID:18641368
  Authors
Boylan B, Gao C, Rathore V, Gill JC, Newman DK, Newman PJ
  Title
Identification of FcgammaRIIa as the ITAM-bearing receptor mediating alphaIIbbeta3 outside-in integrin signaling in human platelets.
  Journal
Blood 112:2780-6 (2008)
DOI:10.1182/blood-2008-02-142125
Related
pathway
rno00590  Arachidonic acid metabolism
rno04015  Rap1 signaling pathway
rno04020  Calcium signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04610  Complement and coagulation cascades
rno05211  Renal cell carcinoma
KO pathway
ko04611   
LinkDB

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