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PAK4
Serine/threonine-protein kinase PAK 4 is an enzyme that in humans is encoded by the PAK4 gene.
PAK4 is one of six members of the PAK family of serine/threonine kinases which are divided into group I (PAK1, PAK2 and PAK3) and group II (PAK4, PAK6 and PAK5/7). PAK4 localizes in sub-cellular domains of the cytoplasm and nucleus. PAK4 regulates cytoskeleton remodeling, phenotypic signaling and gene expression, and affects directional motility, invasion, metastasis, and growth. Similar to PAK1, PAK4-signaling-dependent cellular functions also regulate both physiologic and disease processes such as cancer, as PAK4 is overexpressed and/or hyperstimulated in human cancer, at-large.
PAK4, the founding member of Group II PAK member, was cloned and identified by Minden A. and colleagues in 1998 using a PCR-based strategy from a cDNA library prepared from Jurkett cells.
The group II PAKs have less coding exons compared with group I PAKs, highlights the potential structural and functional differences between two group of PAKs. The human PAK4 is about 57-kb in length with 13 exons. The PAK4 generates 12 transcripts of which 10 coding transcripts are predicted to code proteins of about 438 to 591 amino acids long, while remaining two transcripts are non-coding in nature. In contrast to human PAK4, murine PAK4 contains four transcripts - two coding for 593 amino acids long polypeptides and two are non-coding RNA transcripts.
The core domains of PAK4 include, a kinase domain in the C-terminal region, a p21-binding domain (PBD), and a newly defined auto-inhibitory domain (AID) or an AID-like pseudosubstrate sequence (PS) domain.
PAK4 activity is stimulated by upstream activators and signals, including by HGF, PKD, PKA, CDK5RAP3, and SH3RF2.
In addition to other mechanisms, PAK4 functions are mediated though phosphorylation of its effector proteins, including, LIMK1-Thr508, integrin β5-Ser759/Ser762, p120-catenin-Ser288, superior cervical ganglia 10 (SCG10)-Ser50, GEF-H1-Ser810 β-catenin-Ser675, and Smad2-Ser465.
PAK4 and/or PAK4-dependent signals also modulate the expression of genomic targets, including p57Kip2.
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PAK4
Serine/threonine-protein kinase PAK 4 is an enzyme that in humans is encoded by the PAK4 gene.
PAK4 is one of six members of the PAK family of serine/threonine kinases which are divided into group I (PAK1, PAK2 and PAK3) and group II (PAK4, PAK6 and PAK5/7). PAK4 localizes in sub-cellular domains of the cytoplasm and nucleus. PAK4 regulates cytoskeleton remodeling, phenotypic signaling and gene expression, and affects directional motility, invasion, metastasis, and growth. Similar to PAK1, PAK4-signaling-dependent cellular functions also regulate both physiologic and disease processes such as cancer, as PAK4 is overexpressed and/or hyperstimulated in human cancer, at-large.
PAK4, the founding member of Group II PAK member, was cloned and identified by Minden A. and colleagues in 1998 using a PCR-based strategy from a cDNA library prepared from Jurkett cells.
The group II PAKs have less coding exons compared with group I PAKs, highlights the potential structural and functional differences between two group of PAKs. The human PAK4 is about 57-kb in length with 13 exons. The PAK4 generates 12 transcripts of which 10 coding transcripts are predicted to code proteins of about 438 to 591 amino acids long, while remaining two transcripts are non-coding in nature. In contrast to human PAK4, murine PAK4 contains four transcripts - two coding for 593 amino acids long polypeptides and two are non-coding RNA transcripts.
The core domains of PAK4 include, a kinase domain in the C-terminal region, a p21-binding domain (PBD), and a newly defined auto-inhibitory domain (AID) or an AID-like pseudosubstrate sequence (PS) domain.
PAK4 activity is stimulated by upstream activators and signals, including by HGF, PKD, PKA, CDK5RAP3, and SH3RF2.
In addition to other mechanisms, PAK4 functions are mediated though phosphorylation of its effector proteins, including, LIMK1-Thr508, integrin β5-Ser759/Ser762, p120-catenin-Ser288, superior cervical ganglia 10 (SCG10)-Ser50, GEF-H1-Ser810 β-catenin-Ser675, and Smad2-Ser465.
PAK4 and/or PAK4-dependent signals also modulate the expression of genomic targets, including p57Kip2.