+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Distinct mechanisms determine the patterns of differential activation of H-Ras, N-Ras, K-Ras 4B, and M-Ras by receptors for growth factors or antigen

Distinct mechanisms determine the patterns of differential activation of H-Ras, N-Ras, K-Ras 4B, and M-Ras by receptors for growth factors or antigen

Molecular and Cellular Biology 24(14): 6311-6323

Although GTPases of the Ras family have been implicated in many aspects of the regulation of cells, little is known about the roles of individual family members. Here, we analyzed the mechanisms of activation of H-Ras, N-Ras, K-Ras 4B, and M-Ras by two types of external stimuli, growth factors and ligation of the antigen receptors of B or T lymphocytes (BCRs and TCRs). The growth factors interleukin-3, colony-stimulating factor 1, and epidermal growth factor all preferentially activated M-Ras and K-Ras 4B over H-Ras or N-Ras. Preferential activation of M-Ras and K-Ras 4B depended on the presence of their polybasic carboxy termini, which directed them into high-buoyant-density membrane domains where the activated receptors, adapters, and mSos were also present. In contrast, ligation of the BCR or TCR resulted in activation of H-Ras, N-Ras, and K-Ras 4B, but not M-Ras. This pattern of activation was not influenced by localization of the Ras proteins to membrane domains. Activation of H-Ras, N-Ras, and K-Ras 4B instead depended on the presence of phospholipase C-gamma and RasGRP. Thus, the molecular mechanisms leading to activation of Ras proteins vary with the stimulus and can be influenced by either colocalization with activated receptors or differential sensitivity to the exchange factors activated by a stimulus.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 011967547

Download citation: RISBibTeXText

PMID: 15226433

DOI: 10.1128/MCB.24.14.6311-6323.2004

Related references

Receptors for insulin and other growth factors: rationale for common and distinct mechanisms of cell activation. Clinical and Investigative Medicine. Medecine Clinique et Experimentale 10(5): 475-479, 1987

Hallucinogen actions on 5-HT receptors reveal distinct mechanisms of activation and signaling by G protein-coupled receptors. Aaps Journal 7(4): E871-E884, 2006

Specific PIP2 interactions with inwardly rectifying K+ channels determine distinct activation mechanisms. Society for Neuroscience Abstracts 25(1-2): 1244, 1999

Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages. Journal of Clinical Investigation 92(5): 2408-2418, 1993

Sex and genotype determine the selective activation of neurochemically-distinct mechanisms of swim stress-induced analgesia. Pharmacology, Biochemistry, and Behavior 56(1): 61-66, 1997

Distinct mechanisms of extrathymic T cell tolerance due to differential expression of self antigen. International Immunology 4(5): 581-590, 1992

Differential mechanisms of activation of the Ang peptide receptors AT1, AT2, and MAS: using in silico techniques to differentiate the three receptors. Plos One 8(6): E65307-E65307, 2015

Mechanisms of differential induction of cytokine expression by distinct Toll-like receptors. Journal of Interferon & Cytokine Research 22(Supplement 1): S-56-S-57, 2002

Epidermal growth factor receptors interact with transforming growth factors produced by certain human tumor cells and are distinct from specific membrane receptors for phorbol and ingenol esters. Carcinogenesis; A Comprehensive Survey 7: 443-462, 1982

CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Molecular and Cellular Biology 25(21): 9543-9553, 2005

Activation of distinct receptors affects insulin release by similar mechanisms. Diabetologia 32(7): 483A-484A, 1989

B cell antigen receptor directs the activation of NFAT and NF- B via distinct molecular mechanisms. FASEB Journal 17(7): C203, April 14, 2003

Differential activation of two distinct mechanisms for presynaptic inhibition by a single inhibitory axon. Journal of Neurophysiology 76(6): 3807-3816, 1996

Distinct patterns of activation associated antigen expression are observed in diverse macrophage populations. Journal of Leukocyte Biology (SUPPL 2): 41, 1991

Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. Journal of Immunology 173(1): 657-665, 2004