Cortactin, an 80/85-kilodalton Pp60src Substrate, is a Filamentous Actin-binding Protein Enriched in the Cell Cortex

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 1993 Mar 1

PMID 7680654

Citations 183

Authors

H Wu

J T Parsons

Affiliations

Soon will be listed here.

Abstract

Two related cellular proteins, p80 and p85 (cortactin), become phosphorylated on tyrosine in pp60src-transformed cells and in cells stimulated with certain growth factors. The amino-terminal half of cortactin is comprised of multiple copies of an internal, tandem 37-amino acid repeat. The carboxyl-terminal half contains a distal SH3 domain. We report that cortactin is an F-actin-binding protein. The binding to F-actin is specific and saturable. The amino-terminal repeat region appears to be both necessary and sufficient to mediate actin binding, whereas the SH3 domain had no apparent effect on the actin-binding activity. Cortactin, present in several different cell types, is enriched in cortical structures such as membrane ruffles and lamellipodia. The properties of cortactin indicate that it may be important for microfilament-membrane interactions as well as transducing signals from the cell surface to the cytoskeleton. We suggest the name cortactin, reflecting the cortical subcellular localization and its actin-binding activity.

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References

Singer S . Altered distributions of the cytoskeletal proteins vinculin and alpha-actinin in cultured fibroblasts transformed by Rous sarcoma virus. Proc Natl Acad Sci U S A. 1980; 77(11):6687-91. PMC: 350353. DOI: 10.1073/pnas.77.11.6687. View

Wong S, Reynolds A, Papkoff J . Platelet activation leads to increased c-src kinase activity and association of c-src with an 85-kDa tyrosine phosphoprotein. Oncogene. 1992; 7(12):2407-15. View

Small J, Rinnerthaler G, Hinssen H . Organization of actin meshworks in cultured cells: the leading edge. Cold Spring Harb Symp Quant Biol. 1982; 46 Pt 2:599-611. DOI: 10.1101/sqb.1982.046.01.056. View

Pardee J, Spudich J . Purification of muscle actin. Methods Enzymol. 1982; 85 Pt B:164-81. DOI: 10.1016/0076-6879(82)85020-9. View

Tarone G, Cirillo D, Giancotti F, Comoglio P, Marchisio P . Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes. Exp Cell Res. 1985; 159(1):141-57. DOI: 10.1016/s0014-4827(85)80044-6. View

Holme T, Kellie S, Wyke J, Crawford N . Effect of transformation by Rous sarcoma virus on the character and distribution of actin in Rat-1 fibroblasts: a biochemical and microscopical study. Br J Cancer. 1986; 53(4):465-76. PMC: 2001448. DOI: 10.1038/bjc.1986.74. View

Pollard T, Cooper J . Actin and actin-binding proteins. A critical evaluation of mechanisms and functions. Annu Rev Biochem. 1986; 55:987-1035. DOI: 10.1146/annurev.bi.55.070186.005011. View

Bray D, Heath J, Moss D . The membrane-associated 'cortex' of animal cells: its structure and mechanical properties. J Cell Sci Suppl. 1986; 4:71-88. DOI: 10.1242/jcs.1986.supplement_4.5. View

Pope B, Weeds A . Binding of pig plasma gelsolin to F-actin and partial fractionation into calcium-dependent and calcium-independent forms. Eur J Biochem. 1986; 161(1):85-93. DOI: 10.1111/j.1432-1033.1986.tb10127.x. View

10.

Marchisio P, Cirillo D, Teti A, Tarone G . Rous sarcoma virus-transformed fibroblasts and cells of monocytic origin display a peculiar dot-like organization of cytoskeletal proteins involved in microfilament-membrane interactions. Exp Cell Res. 1987; 169(1):202-14. DOI: 10.1016/0014-4827(87)90238-2. View

11.

Stossel T, Chaponnier C, Ezzell R, Hartwig J, Janmey P, Kwiatkowski D . Nonmuscle actin-binding proteins. Annu Rev Cell Biol. 1985; 1:353-402. DOI: 10.1146/annurev.cb.01.110185.002033. View

12.

Hamaguchi M, Hanafusa H . Association of p60src with Triton X-100-resistant cellular structure correlates with morphological transformation. Proc Natl Acad Sci U S A. 1987; 84(8):2312-6. PMC: 304640. DOI: 10.1073/pnas.84.8.2312. View

13.

Cooper J . Effects of cytochalasin and phalloidin on actin. J Cell Biol. 1987; 105(4):1473-8. PMC: 2114638. DOI: 10.1083/jcb.105.4.1473. View

14.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

15.

Jove R, Hanafusa H . Cell transformation by the viral src oncogene. Annu Rev Cell Biol. 1987; 3:31-56. DOI: 10.1146/annurev.cb.03.110187.000335. View

16.

Smith D, Johnson K . Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988; 67(1):31-40. DOI: 10.1016/0378-1119(88)90005-4. View

17.

Reynolds A, Roesel D, Kanner S, Parsons J . Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol. 1989; 9(2):629-38. PMC: 362640. DOI: 10.1128/mcb.9.2.629-638.1989. View

18.

Glenney Jr J, Zokas L . Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton. J Cell Biol. 1989; 108(6):2401-8. PMC: 2115592. DOI: 10.1083/jcb.108.6.2401. View

19.

Stossel T . From signal to pseudopod. How cells control cytoplasmic actin assembly. J Biol Chem. 1989; 264(31):18261-4. View

20.

Rodaway A, STERNBERG M, Bentley D . Similarity in membrane proteins. Nature. 1989; 342(6250):624. DOI: 10.1038/342624a0. View