Cdc42-MRCK and Rho-ROCK signaling cooperate in myosin phosphorylation and cell invasion (Nature Cell Biology, 7:255-261, March 2005)

報告日期: 2005/10/25
報告時間: 16:00/16:50
報告學生: 邱敏熙
講評老師: 呂增宏
附件下載:

Cdc42–MRCK and Rho–ROCK signalling cooperate in myosin phosphorylation and cell invasion

Nature cell biology, Vol.7, 255-261, March 2005

 

Time:Oct. 25. 2005, 16:00-16:50                Speaker:

Place:Room 602                             Commentator: 老師

Abstract:

Rho family GTPases, of which the best studied members are Cdc42, Rac1 and RhoA, regulate the cytoskeleton and cell migration. Rho signalling increases contractility through Rho-kinase (ROCK)-mediated regulation of myosin-II light chain (MLC2) phosphorylation. Cdc42 signalling has been shown to control cell polarity. The Rho effectors ROCK-I and ROCK-II (ROKβ and ROKα) and the Cdc42 effectors MRCKα and β (myotonic dystrophy kinase-related Cdc42-binding kinase, CDC42BPA and B) share homologous amino-terminal serine-threonine kinase domains that phosphorylate many of the same substrates in vitro. Although the ROCK has been proposed as a physiological regulator of contractility, through myosin -binding subunit (MYPT1, also known as MBS) phosphorylation, but the physiological role of MRCK is not apparent. Recently, the authors had showed that tumor cells can move through a three-dimensional matrix with either a rounded morphology characterized by Rho–ROCK dependence or with an elongated morphology characterized by Rho–ROCK independence. Here the authors show that contractility necessary for elongated morphology and invasion can be generated by Cdc42–MRCK signalling. MRCK cooperates with ROCK in the maintenance of elongated morphology and invasion and either MRCK or ROCK is sufficient for MLC2 phosphorylation, through the inhibitory phosphorylation of myosin phosphatase. The authors suggest that the inhibition of both MRCK and ROCK would inhibit elongated and rounded forms of tumor cell movement .

 

References:

1.      Sahai, E. & Marshall, C. J. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nature Cell Biol. 5, 711–719 (2003).

2.      Wolf, K. et al. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160, 267–277 (2003).