Serine/threonine-protein kinase PAK 2 is an enzyme that in humans is encoded by the PAK2 gene. [5] [6]
PAK2 is one of three members of Group I PAK family of serine/threonine kinases. [7] [8] The PAKs are evolutionary conserved. [9] PAK2 and its cleaved fragment localize in both the cytoplasmic or nuclear compartments. PAK2 signaling modulates apoptosis, [10] endothelial lumen formation, [11] viral pathogenesis, [12] and cancer including, breast, [13] hepatocarcinoma, [14] and gastric [15] and cancer, at-large. [16]
The human PAK2 was identified as a downstream effector of Rac or Cdc42. [7] [8]
The PAK2 gene is about 92.7-kb long. The gene contains 15 exons and generates three alternatively spliced transcripts - two of which code proteins of 524 amino acids and 221 amino acids, while the third one is a 371-bp non-coding RNA transcript(Gene from review) There are two transcripts generated from the murine PAK2 gene, a 5.7-kb transcript coding a 524 amino acids long polypeptide and a 1.2-kb long non-coding RNA transcript.
Similar to PAK1, PAK2 contains a p21-binding domain (PBD) and an auto-inhibitory domain (AID) and exists in an inactive conformation. [16]
The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [17]
The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [18]
PAK2 kinase activity is stimulated by transforming growth factor β in fibroblasts, [19] by proteinase inhibitor alpha2-macroglobulin binding to GRP78 in prostate cancer cells, [20] by its phosphorylation by AMP-activated protein kinase in stem and cancer cells [21] and eryptosis. [22] PAK2 is cleaved through activated caspase-3 in fibroblast and cancer cells exposed to ultraviolet, [23] hyperosmotic shock, [24] and ionizing radiation. [25]
The levels of PAK2 activation in experimental systems are inhibited by synthetic PAK-inhibitors and miRs. For example, FRAX1036 differentially inhibits PAK2 and PAK1 activities; [26] FRAX597 suppresses PAK2 activity in neurofibromatosis type 2 (NF2)-associated tumorigenesis; [27] and miR-23b and miR-137 inhibits PAK2 expression in tumor cells. [28] [29] Insulin stimulation of neuronal cells also antagonizes PAK2 kinase activity, leading to an increased glucose uptake. [30]
PAK2-mediated phosphorylation of merlin at S518 modulates its tumor suppressor activity, [31] c-Jun phosphorylation at T2, T8, T89, T93 and T286 contributes to the growth of growth factor-stimulated melanoma cells, [32] Caspase-7 phosphorylation at S30, T173 and S239 inhibits apoptotic activity in breast cancer cells, [13] Paxillin phosphorylation at S272 and S274 activates ADAM10 protease, [33] and STAT5 phosphorylation at S779 modulates BCL-ABL-mediated leukemogenesis. [34] PAK2 activity negatively regulates the function and expression of c-Myc: PAK2 phosphorylation of c-Myc at T358-S373-T400 inhibits its transactivation function [35] and PAK2 depletion stimulates c-Myc expression during granulocyte-monocyte lineage. [36]
The 2016 version of this article was updated by an external expert under a dual publication model. The corresponding
academic peer reviewed article was published in Gene and can be cited as: Rakesh Kumar, Rahul Sanawar, Xiaodong Li, Feng Li (19 December 2016). "Structure, biochemistry, and biology of PAK kinases". Gene. 605: 20–31. doi: 10.1016/J.GENE.2016.12.014. PMC 5250584. PMID 28007610. |
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Aliases | PAK2, PAK65, PAKgamma, p21 (RAC1) activated kinase 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 605022; MGI: 1339984; HomoloGene: 99711; GeneCards: PAK2; OMA: PAK2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Serine/threonine-protein kinase PAK 2 is an enzyme that in humans is encoded by the PAK2 gene. [5] [6]
PAK2 is one of three members of Group I PAK family of serine/threonine kinases. [7] [8] The PAKs are evolutionary conserved. [9] PAK2 and its cleaved fragment localize in both the cytoplasmic or nuclear compartments. PAK2 signaling modulates apoptosis, [10] endothelial lumen formation, [11] viral pathogenesis, [12] and cancer including, breast, [13] hepatocarcinoma, [14] and gastric [15] and cancer, at-large. [16]
The human PAK2 was identified as a downstream effector of Rac or Cdc42. [7] [8]
The PAK2 gene is about 92.7-kb long. The gene contains 15 exons and generates three alternatively spliced transcripts - two of which code proteins of 524 amino acids and 221 amino acids, while the third one is a 371-bp non-coding RNA transcript(Gene from review) There are two transcripts generated from the murine PAK2 gene, a 5.7-kb transcript coding a 524 amino acids long polypeptide and a 1.2-kb long non-coding RNA transcript.
Similar to PAK1, PAK2 contains a p21-binding domain (PBD) and an auto-inhibitory domain (AID) and exists in an inactive conformation. [16]
The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [17]
The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [18]
PAK2 kinase activity is stimulated by transforming growth factor β in fibroblasts, [19] by proteinase inhibitor alpha2-macroglobulin binding to GRP78 in prostate cancer cells, [20] by its phosphorylation by AMP-activated protein kinase in stem and cancer cells [21] and eryptosis. [22] PAK2 is cleaved through activated caspase-3 in fibroblast and cancer cells exposed to ultraviolet, [23] hyperosmotic shock, [24] and ionizing radiation. [25]
The levels of PAK2 activation in experimental systems are inhibited by synthetic PAK-inhibitors and miRs. For example, FRAX1036 differentially inhibits PAK2 and PAK1 activities; [26] FRAX597 suppresses PAK2 activity in neurofibromatosis type 2 (NF2)-associated tumorigenesis; [27] and miR-23b and miR-137 inhibits PAK2 expression in tumor cells. [28] [29] Insulin stimulation of neuronal cells also antagonizes PAK2 kinase activity, leading to an increased glucose uptake. [30]
PAK2-mediated phosphorylation of merlin at S518 modulates its tumor suppressor activity, [31] c-Jun phosphorylation at T2, T8, T89, T93 and T286 contributes to the growth of growth factor-stimulated melanoma cells, [32] Caspase-7 phosphorylation at S30, T173 and S239 inhibits apoptotic activity in breast cancer cells, [13] Paxillin phosphorylation at S272 and S274 activates ADAM10 protease, [33] and STAT5 phosphorylation at S779 modulates BCL-ABL-mediated leukemogenesis. [34] PAK2 activity negatively regulates the function and expression of c-Myc: PAK2 phosphorylation of c-Myc at T358-S373-T400 inhibits its transactivation function [35] and PAK2 depletion stimulates c-Myc expression during granulocyte-monocyte lineage. [36]
The 2016 version of this article was updated by an external expert under a dual publication model. The corresponding
academic peer reviewed article was published in Gene and can be cited as: Rakesh Kumar, Rahul Sanawar, Xiaodong Li, Feng Li (19 December 2016). "Structure, biochemistry, and biology of PAK kinases". Gene. 605: 20–31. doi: 10.1016/J.GENE.2016.12.014. PMC 5250584. PMID 28007610. |