Recent advances in Ca super(2+)-dependent Ras regulation and cell proliferation

• Published in: Cell calcium (Edinburgh) Vol. 39; no. 2; pp. 101 - 112
• Main Authors: Cook, Simon J, Lockyer, Peter J
• Format: Journal Article
• Language: English
• Published: 01.01.2006
• ISSN: 0143-4160
• DOI: 10.1016/j.ceca.2005.10.014

Our understanding of the mechanisms whereby growth factors stimulate cell proliferation through the Ras pathway stems largely from studies of the canonical pathway involving recruitment of Ras activators and inhibitors to the vicinity of receptor tyrosine kinases via phosphotyrosine-binding adaptor proteins. Ca super(2+) has seldom joined the party, despite the identification of phospholipase C gamma and Ca super(2+) entry as receptor tyrosine kinase-dependent signals. Mechanisms by which Ca super(2+) can directly influence Ras activity have remained relatively elusive. Similarly, the mechanisms whereby Ca super(2+) modulates the cell cycle have been equally murky, and yet there are some interesting parallels in the role of Ras and Ca super(2+) in cell cycle re-entry. This review focuses on a number of novel mechanisms that link Ca super(2+) with the regulation of Ras activity and signaling output. Their collective discovery adds to the complexities of Ras regulation and raises further questions about the role of Ca super(2+) signals in Ras-dependent cell proliferation.