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Gene Review:

TNK2 - tyrosine kinase, non-receptor, 2

Bos taurus

Synonyms: ACK, ACK1

Yang, W. et al., Yang, W. et al., Yang, W. et al., Yang, W. et al., Lin, Q. et al.

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High impact information on ACK1

The nonreceptor tyrosine kinase ACK2, a specific target for Cdc42 and a negative regulator of cell growth and focal adhesion complexes [1].
Overexpression of both wild-type and kinase-defective ACK2 also results in a severe inhibition of cell growth [1].
Activated Cdc42 weakens the interaction between ACK2 and clathrin and thus reverses the ACK2-mediated inhibition of endocytosis [2].
In addition, ACK2 dissolves actin stress fibers and disassembles focal complexes but in a kinase-dependent manner [1].
Using an inducible eukaryotic expression system in fibroblasts, we demonstrate that ACK2 can strongly influence cell shape and growth as well as focal complex formation [1].

Biological context of ACK1

Both anti-integrin beta1 antibody and RGD peptides inhibited the activation of ACK-2 by cell adhesion [3].
Taken together, our data suggest that ACK2 may represent a novel clathrin-assembly protein and participate in the regulation of receptor-mediated endocytosis [2].

Anatomical context of ACK1

However, unlike the focal adhesion kinase, which also is activated by cell adhesion, the activation of ACK-2 is F-actin-independent and does not require cell spreading [3].
Overexpression of ACK2 increases the amount of clathrin present in fractions enriched in clathrin-coated vesicles [2].
In addition, overexpression of ACK-2 in COS-7 cells did not result in the stimulation of extracellular signal-regulated kinase activity but rather activated the c-Jun kinase [3].

Associations of ACK1 with chemical compounds

Cloning and characterization of a novel Cdc42-associated tyrosine kinase, ACK-2, from bovine brain [4].
In addition, ACK-2 was co-immunoprecipitated with integrin beta1 [3].

Regulatory relationships of ACK1

Furthermore, the tyrosine kinase activity of ACK-2 was stimulated both by epidermal growth factor and bradykinin, suggesting that ACK-2 may play a role in the signaling actions of both receptor tyrosine kinases or heterotrimeric G-protein-coupled receptors [4].

Analytical, diagnostic and therapeutic context of ACK1

Co-immunoprecipitation studies indicate that ACK2, clathrin, and SH3PX1 form a complex in cells [5].

References

The nonreceptor tyrosine kinase ACK2, a specific target for Cdc42 and a negative regulator of cell growth and focal adhesion complexes. Yang, W., Lin, Q., Zhao, J., Guan, J.L., Cerione, R.A. J. Biol. Chem. (2001) [Pubmed]
The Cdc42 target ACK2 directly interacts with clathrin and influences clathrin assembly. Yang, W., Lo, C.G., Dispenza, T., Cerione, R.A. J. Biol. Chem. (2001) [Pubmed]
Activation of the Cdc42-associated tyrosine kinase-2 (ACK-2) by cell adhesion via integrin beta1. Yang, W., Lin, Q., Guan, J.L., Cerione, R.A. J. Biol. Chem. (1999) [Pubmed]
Cloning and characterization of a novel Cdc42-associated tyrosine kinase, ACK-2, from bovine brain. Yang, W., Cerione, R.A. J. Biol. Chem. (1997) [Pubmed]
The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation. Lin, Q., Lo, C.G., Cerione, R.A., Yang, W. J. Biol. Chem. (2002) [Pubmed]

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