The serine/threonine kinase PAK4 was identified first as an effector molecule for the Rho GTPase Cdc42. PAK4 differs from other members of the PAK family both in sequence and function. Previously we have shown that an important function of this kinase is to mediate the induction of filopodia in response to activated Cdc42. Studies with a, constitutively active PAK4 mutant have shown that it also has a role in promoting anchorage-independent growth, an important hallmark of oncogenic transformation. Here we show that another function of PAK4 is to protect cells against apoptotic cell death. Expression of wild-type or constitutively active PAK4 delays the onset of apoptosis in response to tumor necrosis factor LY stimulation, UV irradiation, and serum starvation. Consistent with an antiapoptotic function, expression of PAK4 leads to an increase in phosphorylation of the proapoptotic protein Bad and an inhibition of caspase activation.

The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis / N. Gnesutta, J. Qu, A. Minden. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 276:17(2001 Apr), pp. 14414-14419. [10.1074/jbc.M011046200]

The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis

N. Gnesutta
Primo
;
2001

Abstract

The serine/threonine kinase PAK4 was identified first as an effector molecule for the Rho GTPase Cdc42. PAK4 differs from other members of the PAK family both in sequence and function. Previously we have shown that an important function of this kinase is to mediate the induction of filopodia in response to activated Cdc42. Studies with a, constitutively active PAK4 mutant have shown that it also has a role in promoting anchorage-independent growth, an important hallmark of oncogenic transformation. Here we show that another function of PAK4 is to protect cells against apoptotic cell death. Expression of wild-type or constitutively active PAK4 delays the onset of apoptosis in response to tumor necrosis factor LY stimulation, UV irradiation, and serum starvation. Consistent with an antiapoptotic function, expression of PAK4 leads to an increase in phosphorylation of the proapoptotic protein Bad and an inhibition of caspase activation.
NF-kappa-B; ras transformation; survival signals; adapter protein; JNK activation; lim-kinase; family; actin; CDC42; phosphorylation
Settore BIO/10 - Biochimica
Article (author)
File in questo prodotto:
File Dimensione Formato  
GnesuttaJBC2001.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 255.7 kB
Formato Adobe PDF
255.7 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/28769
Citazioni
  • ???jsp.display-item.citation.pmc??? 74
  • Scopus 178
  • ???jsp.display-item.citation.isi??? 169
social impact